6,369 results match your criteria Experimental Hematology[Journal]


Special issue on pluripotent stem cells and hematopoiesis.

Exp Hematol 2019 Feb 12. Epub 2019 Feb 12.

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA; Division of Pediatric Hematology-Oncology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA; Broad Stem Cell Research Center, University of California, Los Angeles, CA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA. Electronic address:

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http://dx.doi.org/10.1016/j.exphem.2019.02.001DOI Listing
February 2019

Vorinostat synergizes with Antioxidant therapy to target Myeloproliferative Neoplasms.

Exp Hematol 2019 Feb 12. Epub 2019 Feb 12.

Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E, Lisboa, Portugal; Centro de Estudos de Doenças Crónicas, CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal; Hospital da Luz, Lisboa, Portugal. Electronic address:

The BCR-ABL-negative myeloproliferative neoplasms (MPN) are driven by JAK-STAT pathway activation but epigenetic alterations also play an important pathophysiological role. These can be pharmacologically manipulated with histone deacetylase inhibitors (HDACis), which have proven to be clinically effective in the treatment of MPN but exhibiting dose-limiting toxicities. The treatment of primary MPN cells with Vorinostat modulates the expression of genes associated with apoptosis, cell cycle, inflammation and signalling. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.02.002DOI Listing
February 2019

Alternative translation initiation generates the N-terminal truncated form of RUNX1 that retains hematopoietic activity.

Exp Hematol 2019 Jan 26. Epub 2019 Jan 26.

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH.

Transcription factor RUNX1 plays a crucial role in hematopoiesis and its activity is tightly regulated at both the transcriptional and posttranslational levels. However, translational control of RUNX1 expression has not been fully understood. In this study, we demonstrated that RUNX1b mRNA is translated from two alternative initiation sites, Met-1 and Met-25, giving full-length RUNX1b and a shorter protein lacking the first 24 amino acids (RUNX1ΔN24). Read More

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http://dx.doi.org/10.1016/j.exphem.2019.01.008DOI Listing
January 2019
1 Read

Erratum to "Engineered humanized bone organs maintain human hematopoiesis in vivo": [Experimental Hematology 61 (2018) 45-51].

Exp Hematol 2019 Jan 26. Epub 2019 Jan 26.

Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland; International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan.

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http://dx.doi.org/10.1016/j.exphem.2019.01.007DOI Listing
January 2019

Disease modeling of bone marrow failure syndromes using iPSC-derived hematopoietic stem progenitor cells.

Exp Hematol 2019 Jan 19. Epub 2019 Jan 19.

Hematology/Respiratory Medicine, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. Electronic address:

The plasticity of induced pluripotent stem cells (iPSCs) with the potential to differentiate into virtually any type of cells and the feasibility of generating hematopoietic stem progenitor cells (HSPCs) from patient-derived iPSCs (iPSC-HSPCs) has many potential applications in hematology. For example, iPSC-HSPCs are being used for leukemogenesis studies and their application in various cell replacement therapies is being evaluated. The use of iPSC-HSPCs can now provide an invaluable resource for the study of diseases associated with the destruction of HSPCs, such as bone marrow failure syndromes (BMFSs). Read More

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http://dx.doi.org/10.1016/j.exphem.2019.01.006DOI Listing
January 2019
6 Reads

Application of induced pluripotent stem cells to primary immunodeficiency diseases.

Exp Hematol 2019 Jan 19. Epub 2019 Jan 19.

Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.

Primary immunodeficiency diseases (PIDs) are a heterogeneous group of rare immune disorders with genetic causes. Effective treatments using hematopoietic stem cells or pharmaceutical agents have been around for decades. However, for many patients, these treatment options are ineffective, partly because the rarity of these PIDs complicates the diagnosis and therapy. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.01.005DOI Listing
January 2019
3 Reads

Modeling malignancies using induced pluripotent stem cells: from chronic myeloid leukemia to hereditary cancers.

Exp Hematol 2019 Jan 16. Epub 2019 Jan 16.

INSERM UMR-S 935 and ESTeam Paris Sud, Université Paris Sud, Villejuif, France; INGESTEM National iPSC Infrastructure, Villejuif, France.

Over the last decade, the possibility of reprogramming malignant cells to a pluripotent state has been achieved in several hematological malignancies, including myeloproliferative neoplasms, myelodysplastic syndromes, and chronic myeloid leukemia (CML). It has been shown that it is readily possible to generate induced pluripotent stem cells (iPSCs) from several types of primary CML cells and to generate progenitors and differentiated cells with variable efficiency. Although these experiments have brought some new insights in the understanding of CML pathophysiology, the ultimate goal of generating induced leukemic stem cells (LSCs) with long-term multilineage potential has not yet been demonstrated. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.01.003DOI Listing
January 2019
2 Reads

Induced pluripotent stem cell modeling of malignant hematopoiesis.

Exp Hematol 2019 Jan 16. Epub 2019 Jan 16.

Department of Medicine, Division of Hematology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA. Electronic address:

The ability to epigenetically reprogram differentiated somatic cells to pluripotency resulting in the discovery of induced pluripotent stem cells (iPSCs), has unlocked fundamental biologic insights into numerous genetic diseases. These insights have resulted from the key property of iPSCs to differentiate into all cell lineages in an unlimited manner while maintaining the genetic identity of the originating cell. iPSCs have been utilized to investigate both monogenic and complex genetic disorders spanning hereditary and acquired diseases. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.01.002DOI Listing
January 2019

Sphingosine-1-phosphate signaling modulates terminal erythroid differentiation through the regulation of mitophagy.

Exp Hematol 2019 Jan 16. Epub 2019 Jan 16.

Cancer Science Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Kumamoto University, International Research Center for Medical Sciences, Kumamoto, Japan. Electronic address:

Erythropoiesis is a highly coordinated stepwise process involving the progressive clearance of mitochondria via mitophagy. Based on the expression of several macroautophagy and mitophagy specific genes, we identified a sequential change in the transcriptional pattern during terminal erythroid differentiation. Because erythroid cells are a major source of serum sphingosine-1-phosphate, we analyzed the role of sphingolipid signaling in erythropoiesis and demonstrate that sphingosine kinase activity promotes terminal erythroid differentiation by regulating the expression of key mitophagy genes Pink1 and Bnip3l/Nix. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.01.004DOI Listing
January 2019
3 Reads
2.475 Impact Factor

USP44 is dispensable for normal hematopoietic stem cell function, lymphocyte development, and B-cell-mediated immune response in a mouse model.

Exp Hematol 2019 Jan 9. Epub 2019 Jan 9.

Department of Physiology, McGill University, Montreal, QC, Canada; McGill University Centre on Complex Traits, McGill University, Montreal, QC, Canada. Electronic address:

Ubiquitin-specific protease 44 (USP44) is a nuclear protein with deubiquitinase (DUB) catalytic activity that has been implicated as an important regulator of cell cycle progression, gene expression, and genomic stability. Dysregulation in the molecular machinery controlling cell proliferation, gene expression, and genomic stability in human or mouse is commonly linked to hematopoietic dysfunction, immunodeficiency, and cancer. We therefore set out to explore the role of USP44 in hematopoietic and immune systems through characterization of a Usp44-deficient mouse model. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.01.001DOI Listing
January 2019
1 Read
2.475 Impact Factor

Human iPSC-based model of severe congenital neutropenia reveals elevated UPR and DNA damage in CD34 cells preceding leukemic transformation.

Exp Hematol 2019 Jan 4. Epub 2019 Jan 4.

Department of Oncology, Hematology, Immunology, Rheumatology, and Pulmonology, University Hospital Tuebingen, Tuebingen, Germany. Electronic address:

We describe the establishment of an embryoid-body-based protocol for hematopoietic/myeloid differentiation of human induced pluripotent stem cells that allows the generation of CD34 cells or mature myeloid cells in vitro. Using this model, we were able to recapitulate the defective granulocytic differentiation in patients with severe congenital neutropenia (CN), an inherited preleukemia bone marrow failure syndrome. Importantly, in vitro maturation arrest of granulopoiesis was associated with an elevated unfolded protein response (UPR) and enhanced expression of the cell cycle inhibitor p21. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.12.006DOI Listing
January 2019
4 Reads

Compounds targeting class II histone deacetylases do not cause panHDACI-associated impairment of megakaryocyte differentiation.

Exp Hematol 2019 Jan 4. Epub 2019 Jan 4.

Department of Biology, Drexel University, Philadelphia, PA; Sidney Kimmel Cancer Center, Philadelphia, PA. Electronic address:

Histone deacetylase inhibitors (HDACIs) have demonstrated effectiveness against lymphomas and myelomas in clinical practice. However, common to all currently approved broad-acting HDACIs (panHDACIs) is dose-limiting thrombocytopenia, which has prevented wider use in cancer therapy. Using CD34 hematopoietic stem cells (HSCs), we show that megakaryocyte (MK) cell maturation and differentiation is impaired by panHDACIs correlating to clinical thrombocytopenia. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.12.007DOI Listing
January 2019
5 Reads

Development of innate immune cells from human pluripotent stem cells.

Exp Hematol 2019 Jan 4. Epub 2019 Jan 4.

Department of Medicine, Division of Regenerative Medicine, University of California San Diego, CA. Electronic address:

Mouse and human pluripotent stem cells have been widely used to study the development of the hematopoietic and immune systems. Although not all cells can be derived with the same efficiency, immune cells such as natural killer (NK) cells and macrophages can be easily produced from PSCs to enable development of new cell-based therapies. NK cells and macrophages are part of the innate immune system, the first line of defense against malignancies and infectious disease. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.12.005DOI Listing
January 2019

Targeting cell-bound MUC1 on myelomonocytic, monocytic leukemias and phenotypically defined leukemic stem cells with anti-SEA module antibodies.

Exp Hematol 2019 Feb 26;70:97-108. Epub 2018 Dec 26.

School of Molecular Cell Biology and Biotechnology, Tel Aviv University, Ramat Aviv, Israel.

Cell surface molecules aberrantly expressed or overexpressed by myeloid leukemic cells represent potential disease-specific therapeutic targets for antibodies. MUC1 is a polymorphic glycoprotein, the cleavage of which yields two unequal chains: a large extracellular α subunit containing a tandem repeat array bound in a strong noncovalent interaction to a smaller β subunit containing the transmembrane and cytoplasmic domains. Because the α-chain can be released from the cell-bound domains of MUC1, agents directed against the α-chain will not effectively target MUC1 cells. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.12.002DOI Listing
February 2019
6 Reads

Functional interdependence of hematopoietic stem cells and their niche in oncogene promotion of myeloproliferative neoplasms: the 159th biomedical version of "it takes two to tango".

Exp Hematol 2019 Feb 26;70:24-30. Epub 2018 Dec 26.

School of Medicine, Stony Brook University, Stony Brook, New York. Electronic address:

The role of stem cells in normal and neoplastic hematopoiesis is well established. However, neither normal nor neoplastic hematopoietic stem cells (HSCs) develop in isolation and accumulating evidence indicates that a critical developmental role is played by the perivascular "niche." The cellular, humoral, and cell surface contacts that provide the proper environment for HSC survival, proliferation, and differentiation are becoming increasingly better understood. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.12.004DOI Listing
February 2019

From Pluripotent Stem Cells to T cells.

Exp Hematol 2018 Dec 24. Epub 2018 Dec 24.

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA; Division of Pediatric Hematology-Oncology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA; Broad Stem Cell Research Center, University of California, Los Angeles, CA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA. Electronic address:

The generation of T cells from human pluripotent stem cells (PSCs) opens a valuable experimental window into developmental hematopoiesis and raises the possibility of a new therapeutic approach for T-cell immunotherapy. After directing PSCs through mesoderm and early hematopoietic developmental stages, commitment to the T-cell lineage has been achieved by several groups using coculture with stromal cells that express a notch ligand, recapitulating the critical signals that initiate the first stages of normal T-cell differentiation in the thymus. However, positive selection and the production of mature T cells from human PSCs have been limited to date. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.12.001DOI Listing
December 2018
3 Reads

MISTRG mice support engraftment and assessment of nonhuman primate hematopoietic stem and progenitor cells.

Exp Hematol 2019 Feb 25;70:31-41.e1. Epub 2018 Dec 25.

Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Immunology, University of Washington School of Medicine, Seattle, WA. Electronic address:

Preclinical feasibility, safety, and efficacy testing of hematopoietic stem cell (HSC)-mediated gene therapy approaches is commonly performed in large-animal models such as nonhuman primates (NHPs). Here, we wished to determine whether mouse models would allow engraftment of NHP HSPCs, which would enable more facile and less costly evaluation of promising strategies. In this study, we comprehensively tested two mouse strains for the engraftment of NHP CD34 hematopoietic stem and progenitor cells (HSPCs). Read More

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http://dx.doi.org/10.1016/j.exphem.2018.12.003DOI Listing
February 2019

Emerging role of noncanonical polycomb repressive complexes in normal and malignant hematopoiesis.

Exp Hematol 2018 Dec 26;68:10-14. Epub 2018 Oct 26.

Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan. Electronic address:

Polycomb group (PcG) proteins are the key epigenetic regulators of normal hematopoiesis and the dysregulation of their functions is closely involved in the pathogenesis of hematological malignancies. These proteins function in the multimeric complexes called polycomb repressive complex (PRC) 1 and 2. In addition to canonical PRC1, four noncanonical PRC1 complexes have been identified. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.10.008DOI Listing
December 2018
9 Reads

Smc3 is required for mouse embryonic and adult hematopoiesis.

Exp Hematol 2019 Feb 13;70:70-84.e6. Epub 2018 Dec 13.

Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:

SMC3 encodes a subunit of the cohesin complex that has canonical roles in regulating sister chromatids segregation during mitosis and meiosis. Recurrent heterozygous mutations in SMC3 have been reported in acute myeloid leukemia (AML) and other myeloid malignancies. In this study, we investigated whether the missense mutations in SMC3 might have dominant-negative effects or phenocopy loss-of-function effects by comparing the consequences of Smc3-deficient and -haploinsufficient mouse models. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.11.008DOI Listing
February 2019
8 Reads

Arterial identity of hemogenic endothelium: a key to unlock definitive hematopoietic commitment in hPSC cultures.

Exp Hematol 2018 Nov 28. Epub 2018 Nov 28.

National Primate Research Center, University of Wisconsin Graduate School, Madison, WI, USA.

Human pluripotent stem cells (hPSCs) have been suggested as a potential source for the de novo production of blood cells for transfusion, immunotherapies, and transplantation. However, even with advanced hematopoietic differentiation methods, the primitive and myeloid-restricted waves of hematopoiesis dominate in hPSC differentiation cultures, whereas cell surface markers to distinguish these waves of hematopoiesis from lympho-myeloid hematopoiesis remain unknown. In the embryo, hematopoietic stem cells (HSCs) arise from hemogenic endothelium (HE) lining arteries, but not veins. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.11.007DOI Listing
November 2018
3 Reads

Modeling myeloid malignancies with patient-derived iPSCs.

Exp Hematol 2018 Nov 24. Epub 2018 Nov 24.

Department of Oncological Sciences, Department of Medicine, Tisch Cancer Institute, and Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

Modeling human diseases with patient-derived induced pluripotent stem cells (iPSCs) offers unique research opportunities and is particularly attractive for hematology research. Whereas monogenic inherited blood diseases featured prominently among the first proof-of-principle studies of iPSC modeling, malignant hematologic disorders have been off to a slower start. This has been due to challenges in the derivation of iPSCs from cancer cells and the need to establish robust differentiation protocols and to standardize phenotypic assays of iPSC-derived hematopoiesis. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.11.006DOI Listing
November 2018
5 Reads

A track of the clones: new developments in cellular barcoding.

Exp Hematol 2018 Dec 15;68:15-20. Epub 2018 Nov 15.

Institute Curie, PSL Research Univeristy, CNRS UMR168, Paris, France; Sorbonne Universités, UPMC University. Electronic address:

International experts from multiple disciplines gathered at Homerton College in Cambridge, UK from September 12-14, 2018 to consider recent advances and emerging opportunities in the clonal tracking of hematopoiesis in one of a series of StemCellMathLab workshops. The group included 35 participants with experience in the fields of theoretical and experimental aspects of clonal tracking, and ranged from doctoral students to senior professors. Data from a variety of model systems and from clinical gene therapy trials were discussed, along with strategies for data analysis and sharing and challenges arising due to underlying assumptions in data interpretation and communication. Read More

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December 2018
12 Reads

Message from the Editor.

Authors:
Connie Eaves

Exp Hematol 2018 Dec 12;68. Epub 2018 Nov 12.

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http://dx.doi.org/10.1016/j.exphem.2018.11.004DOI Listing
December 2018

The case for plerixafor to replace filgrastim as the optimal agent to mobilize peripheral blood donors for allogeneic hematopoietic cell transplantation.

Exp Hematol 2019 Feb 11;70:1-9. Epub 2018 Nov 11.

Division of Pediatric Hematology/Oncology/Blood and Marrow Transplant, British Columbia Children's Hospital, Vancouver, British Columbia, Canada; Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada; Michael Cuccione Childhood Cancer Research Program, British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada. Electronic address:

Granulocyte colony-stimulating factor (G-CSF)-stimulated peripheral blood progenitor cells (G-PBs) from either a related or unrelated donor continue to be the preferred donor source for most allogeneic hematopoietic cell transplantation (HCT). Recently, the American Society for Blood and Marrow Transplantation has recommended marrow instead of G-PBs as an unrelated graft source due to its lower rate of chronic graft-versus-host disease (cGVHD). However, the use of marrow is limited by both clinical considerations (slower rate of engraftment and increased donor morbidity) and logistical considerations (use of operating room resources and increased physician utilization), so this recommendation has not been widely adopted. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.11.003DOI Listing
February 2019
11 Reads
2.480 Impact Factor

Deferasirox selectively induces cell death in the clinically relevant population of leukemic CD34CD38 cells through iron chelation, induction of ROS, and inhibition of HIF1α expression.

Exp Hematol 2019 Feb 8;70:55-69.e4. Epub 2018 Nov 8.

Felsenstein Medical Research Center, Beilinson Hospital, Rabin Medical Center, Petah-Tikva, Israel. Electronic address:

Despite a high remission rate after therapy, only 40-50% of acute myeloid leukemia (AML) patients survive 5 years after diagnosis. The main cause of treatment failure is thought to be insufficient eradication of CD34CD38 AML cells. In order to induce preferential cell death in CD34CD38 AML cells, two separate events may be necessary: (1) inhibition of survival signals such as nuclear factor kappa-beta (NF-κB) and (2) induction of stress responses such as the oxidative stress response. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.10.010DOI Listing
February 2019
12 Reads

MIR-144-mediated NRF2 gene silencing inhibits fetal hemoglobin expression in sickle cell disease.

Exp Hematol 2019 Feb 6;70:85-96.e5. Epub 2018 Nov 6.

Department of Pediatrics, Augusta University, Augusta, GA, USA; Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA, USA. Electronic address:

Inherited genetic modifiers and pharmacologic agents that enhance fetal hemoglobin (HbF) expression reverse the clinical severity of sickle cell disease (SCD). Recent efforts to develop novel strategies of HbF induction include discovery of molecular targets that regulate γ-globin gene transcription and translation. The purpose of this study was to perform genome-wide microRNA (miRNA) analysis to identify genes associated with HbF expression in patients with SCD. Read More

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February 2019
12 Reads

Modeling human RNA spliceosome mutations in the mouse: not all mice were created equal.

Exp Hematol 2019 Feb 6;70:10-23. Epub 2018 Nov 6.

St. Vincent's Institute, Fitzroy, Victoria 3065, Australia; Department of Medicine, St. Vincent's Hospital, University of Melbourne, Fitzroy, Victoria 3065, Australia; Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria 3000, Australia. Electronic address:

Myelodysplastic syndromes (MDS) and related myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are clonal stem cell disorders, primarily affecting patients over 65 years of age. Mapping of the MDS and MDS/MPN genome identified recurrent heterozygous mutations in the RNA splicing machinery, with the SF3B1, SRSF2, and U2AF1 genes being frequently mutated. To better understand how spliceosomal mutations contribute to MDS pathogenesis in vivo, numerous groups have sought to establish conditional murine models of SF3B1, SRSF2, and U2AF1 mutations. Read More

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February 2019
13 Reads

Membrane-potential compensation reveals mitochondrial volume expansion during HSC commitment.

Exp Hematol 2018 Dec 3;68:30-37.e1. Epub 2018 Nov 3.

Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY, USA; Departments of Cell Biology and Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Albert Einstein Cancer Center and Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address:

Proper control of mitochondrial function is a key factor in the maintenance of hematopoietic stem cells (HSCs). Mitochondrial content is commonly measured by staining with fluorescent cationic dyes. However, dye staining can be affected, not only by xenobiotic efflux pumps, but also by dye intake, which is dependent on the negative charge of mitochondria. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350772PMC
December 2018
7 Reads

CircPAN3 mediates drug resistance in acute myeloid leukemia through the miR-153-5p/miR-183-5p-XIAP axis.

Exp Hematol 2019 Feb 3;70:42-54.e3. Epub 2018 Nov 3.

Department of Pathology, Fujian Provincial Hospital; Provincial Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.

The contribution and role of circular RNAs (circRNAs) in mediating chemoresistance in acute myeloid leukemia (AML) are still poorly understood and need further investigation. In this study, we established a doxorubicin (ADM)-resistant THP-1 AML cell line (THP-1/ADM). A high-throughput microarray was used to identify circRNA expression profiles of THP-1/ADM cells and naive THP-1 cells. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.10.011DOI Listing
February 2019
16 Reads

RUNX1 and the endothelial origin of blood.

Exp Hematol 2018 Dec 31;68:2-9. Epub 2018 Oct 31.

Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

The transcription factor RUNX1 is required in the embryo for formation of the adult hematopoietic system. Here, we describe the seminal findings that led to the discovery of RUNX1 and of its critical role in blood cell formation in the embryo from hemogenic endothelium (HE). We also present RNA-sequencing data demonstrating that HE cells in different anatomic sites, which produce hematopoietic progenitors with dissimilar differentiation potentials, are molecularly distinct. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.10.009DOI Listing
December 2018
10 Reads
2.480 Impact Factor

Effect of circadian variation on neutrophil mobilization to the peripheral blood in benign constitutional neutropenia.

Exp Hematol 2019 Jan 25;69:22-26. Epub 2018 Oct 25.

University Hospital, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Benign constitutional neutropenia (BCN) is an asymptomatic condition characterized by mild chronic neutropenia in patients with no history of recurrent infections. Most patients are referred for further testing, increasing health care costs. We present an alternative form of assessment of individuals with BCN based on neutrophil circadian variation. Read More

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January 2019
3 Reads

Characterization of inv(3) cell line OCI-AML-20 with stroma-dependent CD34 expression.

Exp Hematol 2019 Jan 22;69:27-36. Epub 2018 Oct 22.

Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Ontario, Canada. Electronic address:

Acute myeloid leukemia (AML) is a complex, heterogeneous disease with variable outcomes following curative intent chemotherapy. AML with inv(3) is a genetic subgroup characterized by a very low response rate to current induction type chemotherapy and thus has among the worst long-term survivorship of the AMLs. Here, we describe OCI-AML-20, a new AML cell line with inv(3) and deletion of chromosome 7; the latter is a common co-occurrence in inv(3) AML. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.10.006DOI Listing
January 2019
14 Reads

Establishment and characterization of immortalized erythroid progenitor cell lines derived from a common cell source.

Exp Hematol 2019 Jan 13;69:11-16. Epub 2018 Oct 13.

Department of Research and Development, Central Blood Institute, Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan.

Immortalized erythroid progenitor cell lines, which exhibit potential for enucleated red blood cell (RBC) production, are expected to serve as an in vitro source of RBCs. These erythroid progenitor cell lines have previously been established from a variety of sources; however, large numbers of cell lines have not been established, characterized, and compared from a common cell source. In the present study, 37 cell lines were established from human bone marrow cells from a single donor. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.10.005DOI Listing
January 2019
17 Reads

Loss of EfnB1 in the osteogenic lineage compromises their capacity to support hematopoietic stem/progenitor cell maintenance.

Exp Hematol 2019 Jan 13;69:43-53. Epub 2018 Oct 13.

Mesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia; Cancer Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia. Electronic address:

The bone marrow stromal microenvironment contributes to the maintenance and function of hematopoietic stem/progenitor cells (HSPCs). The Eph receptor tyrosine kinase family members have been implicated in bone homeostasis and stromal support of HSPCs. The present study examined the influence of EfnB1-expressing osteogenic lineage on HSPC function. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.10.004DOI Listing
January 2019
1 Read
2.480 Impact Factor

Interleukin-18 plays a dispensable role in murine and likely also human bone marrow failure.

Exp Hematol 2019 Jan 12;69:54-64.e2. Epub 2018 Oct 12.

Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.

Interleukin-18 (IL-18), also known as interferon-gamma (IFN-γ)-inducing factor, is involved in Th1 responses and regulation of immunity. Accumulating evidence implicates IL-18 in autoimmune diseases, but little is known of its role in acquired aplastic anemia (AA), the immune-mediated destruction of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs). IL-18 protein levels were significantly elevated in sera of severe AA (SAA) patients, including both responders and nonresponders assayed before treatment, and decreased after treatment. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309608PMC
January 2019
12 Reads

TCF4 promotes erythroid development.

Exp Hematol 2019 Jan 10;69:17-21.e1. Epub 2018 Oct 10.

Department of Hematology, University Medical Centre Groningen, Groningen, The Netherlands.

Transcription factor 4 (TCF4) is implicated in lymphoid cell differentiation and its expression predicts outcome in acute myeloid leukemia. Here, we investigated the role of TCF4 in myelopoiesis. Overexpression of TCF4 (TCF4) in umbilical cord blood (UCB) cells resulted in a twofold increase in erythroid colony forming units (CFU-Es), whereas knock-down (KD) of TCF4 (TCF4) caused a dramatic decrease in the number of erythroid colonies. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0301472X183085
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http://dx.doi.org/10.1016/j.exphem.2018.10.002DOI Listing
January 2019
3 Reads

Distinct pathways affected by menin versus MLL1/MLL2 in MLL-rearranged acute myeloid leukemia.

Exp Hematol 2019 Jan 10;69:37-42. Epub 2018 Oct 10.

Department of Pediatrics, University of Colorado, Denver/Anschutz Medical Campus. Aurora, CO, USA; Department of Pharmacology, University of Colorado, Denver/Anschutz Medical Campus. Aurora, CO, USA. Electronic address:

Disrupting the protein-protein interaction for molecularly targeted cancer therapeutics can be a challenging but promising strategy. Compounds that disrupt the interaction between menin, a chromatin-binding protein, and oncogenic mixed lineage leukemia fusion proteins (MLL-FPs) have shown significant promise in preclinical models of leukemia and have a high degree of selectivity for leukemia versus normal hematopoietic cells. Biochemical and structural studies demonstrate that, in addition to disrupting the menin-MLL-FP interaction, such compounds also inhibit menin-MLL1, menin-MLL2, and other menin-interacting proteins. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.10.001DOI Listing
January 2019
3 Reads

Aptamer-based proteomics of serum and plasma in acquired aplastic anemia.

Exp Hematol 2018 Dec 9;68:38-50. Epub 2018 Oct 9.

Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD, USA.

Single-stranded oligonucleotides containing deoxyuridine are aptamers (SOMAmers) that can bind proteins with high specificity and affinity and slow dissociation rates. SOMAscan, an aptamer-based proteomic technology, allows measurement of more than 1,300 proteins simultaneously for the identification of new disease biomarkers. The aim of the present study was to identify new serum and plasma protein markers for diagnosis of acquired aplastic anemia (AA) and response to immunosuppressive therapies (IST). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0301472X183084
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http://dx.doi.org/10.1016/j.exphem.2018.09.008DOI Listing
December 2018
20 Reads
2.480 Impact Factor

Skewed ratio between type 1 and type 2 calreticulin mutations in essential thrombocytosis patients with concomitant Janus kinase 2 V617F mutation.

Exp Hematol 2018 Dec 4;68:62-65. Epub 2018 Oct 4.

Department of Hematology, Aarhus University Hospital, Aarhus, Denmark. Electronic address:

Detection of somatic mutations in cardinal driver genes is a strong argument for diagnosis in classical Philadelphia-negative myeloproliferative neoplasms (MPNs). Driver mutations in Janus kinase 2 (JAK2), calreticulin (CALR), and thrombopoietin receptor (MPL), are generally considered mutually exclusive, but several reports have suggested that they coexist in a small subgroup of patients. In this study, we retrospectively searched for CALR mutations in 136 suspected MPN patients with low allelic burden (≤5%) JAK2 V617F. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.09.007DOI Listing
December 2018
12 Reads

A rare subgroup of leukemia stem cells harbors relapse-inducing potential in acute lymphoblastic leukemia.

Exp Hematol 2019 Jan 24;69:1-10. Epub 2018 Sep 24.

Research Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Center Munich, German Center for Environmental Health (HMGU), Munich, Germany; Department of Pediatrics, Dr. von Hauner Childrens Hospital, Ludwig Maximilians University, Munich, Germany; German Consortium for Translational Cancer Research (DKTK), Partnering Site Munich, Munich, Germany. Electronic address:

After initially successful chemotherapy, relapse frequently jeopardizes the outcome of patients with acute leukemia. Because of their adverse characteristics of self-renewal and dormancy, leukemia stem cells have been hypothesized to play a critical role in resistance to antiproliferative chemotherapy and the development of relapse. The high abundance of stem-like cells in acute lymphoblastic leukemia (ALL), however, suggests that not all leukemia-initiating cells carry these adverse characteristics, complicating the biological characterization of relapse-inducing cells in this malignancy. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0301472X183080
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http://dx.doi.org/10.1016/j.exphem.2018.09.006DOI Listing
January 2019
11 Reads

The Human Cell Atlas bone marrow single-cell interactive web portal.

Exp Hematol 2018 Dec 21;68:51-61. Epub 2018 Sep 21.

Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio, USA; Department of Biomedical Informatics, University of Cincinnati, Cincinnati, OH, USA. Electronic address:

The Human Cell Atlas (HCA) is expected to facilitate the creation of reference cell profiles, marker genes, and gene regulatory networks that will provide a deeper understanding of healthy and disease cell types from clinical biospecimens. The hematopoietic system includes dozens of distinct, transcriptionally coherent cell types, including intermediate transitional populations that have not been previously described at a molecular level. Using the first data release from the HCA bone marrow tissue project, we resolved common, rare, and potentially transitional cell populations from over 100,000 hematopoietic cells spanning 35 transcriptionally coherent groups across eight healthy donors using emerging new computational approaches. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296228PMC
December 2018
5 Reads

Upregulated microRNA-146a expression induced by granulocyte colony-stimulating factor enhanced low-dosage chemotherapy response in aged acute myeloid leukemia patients.

Exp Hematol 2018 Dec 9;68:66-79.e3. Epub 2018 Sep 9.

Department of Hematology, South Campus, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, P.R. China. Electronic address:

The selection of chemotherapy regimen for elderly patients with acute myeloid leukemia (AML) remains challenging. Here, we report that granulocyte colony-stimulating factor (G-CSF) upregulates the expression of microRNA (miR)-146a in a nuclear factor kappaB-dependent manner, leading to direct decreases in the expression of the target proteins CXCR4 and Smad4 in AML cells in vitro. The reduction in CXCR4 expression suppressed the migration abilities of leukemia cells. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0301472X183079
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http://dx.doi.org/10.1016/j.exphem.2018.09.002DOI Listing
December 2018
16 Reads

Platelet engraftment after allogenic stem cell transplantation is monitored by digital polymerase chain reaction without interference by platelet support.

Exp Hematol 2018 Dec 6;68:21-29. Epub 2018 Sep 6.

DRK-Blutspendedienst NSTOB, Institut Springe, Springe, Germany.

Platelet engraftment after allogeneic hematopoietic stem cell transplantation is conventionally monitored by daily platelet counts. Platelet transfusions are frequently required and obscure the detection of platelet engraftment. Digital polymerase chain reaction (ddPCR) of mitochondrial DNA isolated from platelets reliably quantifies circulating platelets derived from the stem cell graft and allows us to distinguish them from transfused single-donor apheresis platelets. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.08.007DOI Listing
December 2018
1 Read

miR-217 sensitizes chronic myelogenous leukemia cells to tyrosine kinase inhibitors by targeting pro-oncogenic anterior gradient 2.

Exp Hematol 2018 Dec 5;68:80-88.e2. Epub 2018 Sep 5.

Department of Hematology, Fukushima Medical University, Fukushima, Japan. Electronic address:

BCR-ABL1-independent mechanisms had been thought to mediate drug resistance to tyrosine kinase inhibitors (TKIs) in patients with chronic myelogenous leukemia (CML). The pro-oncogenic anterior gradient 2 (AGR2) mediates drug resistance of cancer cells. In this study, we observed an increased level of AGR2 in TKI-resistant CML cells. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.09.001DOI Listing
December 2018
3 Reads

Ponatinib evaluation and safety in real-life chronic myelogenous leukemia patients failing more than two tyrosine kinase inhibitors: the PEARL observational study.

Exp Hematol 2018 11 5;67:41-48. Epub 2018 Sep 5.

Hematology Department, Centre Léon Bérard, Lyon, France; INSERM U1052, CRCL, Lyon, France; French Group of CML (Fi-LMC), Institut Bergonié, Bordeaux, France. Electronic address:

Ponatinib represents a remarkable progress in the treatment of heavily pretreated chronic myelogenous leukemia (CML) and de novo Philadelphia chromosome-positive ALL patients despite significant toxicity in clinical trials. To date, "real-life" data remain few and the use of ponatinib in this setting and its consequences remain mostly unknown. We report, within a national observational study, the use of ponatinib in unselected CML patients who had previously failed ≥2 lines of tyrosine kinase inhibitor (TKI) therapy (or one line if an Abelson (ABL) mutation was identified), in real-life conditions (2013-2014) in a compassionate program. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.08.006DOI Listing
November 2018
37 Reads

Long noncoding RNA HOTAIR promotes the self-renewal of leukemia stem cells through epigenetic silencing of p15.

Exp Hematol 2018 11 30;67:32-40.e3. Epub 2018 Aug 30.

Department of Pathogenic Biology and Immunology, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China. Electronic address:

Acute myeloid leukemia (AML) is a heterogeneous hematopoietic disorder initiated from a small subset of leukemia stem cell (LSC), which presents unrestricted self-renewal and proliferation. Long non-coding RNA HOTAIR is abundantly expressed and plays oncogenic roles in solid cancer and AML. However, whether HOTAIR regulates the self-renewal of LSC is largely unknown. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0301472X183075
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http://dx.doi.org/10.1016/j.exphem.2018.08.005DOI Listing
November 2018
8 Reads

Oral administration of the LSD1 inhibitor ORY-3001 increases fetal hemoglobin in sickle cell mice and baboons.

Exp Hematol 2018 11 17;67:60-64.e2. Epub 2018 Aug 17.

Jesse Brown VA Medical Center, Chicago, IL, USA; Section of Hematology/Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA. Electronic address:

Increased levels of fetal hemoglobin (HbF) lessen the severity of symptoms and increase the life span of patients with sickle cell disease (SCD). More effective strategies to increase HbF are needed because the current standard of care, hydroxyurea, is not effective in a significant proportion of patients. Treatment of the millions of patients projected worldwide would best be accomplished with an orally administered drug therapy that increased HbF. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.08.003DOI Listing
November 2018
3 Reads

Comparative utility of NRG and NRGS mice for the study of normal hematopoiesis, leukemogenesis, and therapeutic response.

Exp Hematol 2018 11 17;67:18-31. Epub 2018 Aug 17.

Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA; James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA; Department of Medicine, University of Louisville, Louisville, KY, USA. Electronic address:

Cell-line-derived xenografts (CDXs) or patient-derived xenografts (PDXs) in immune-deficient mice have revolutionized our understanding of normal and malignant human hematopoiesis. Transgenic approaches further improved in vivo hematological research, allowing the development of human-cytokine-producing mice, which show superior human cell engraftment. The most popular mouse strains used in research, the NOG (NOD. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200600PMC
November 2018
10 Reads

Epigenetic modification enhances the cytotoxicity of busulfan and4-hydroperoxycyclophosphamide in AML cells.

Exp Hematol 2018 11 10;67:49-59.e1. Epub 2018 Aug 10.

Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

The combination of the DNA-alkylating agents busulfan (Bu) and cyclophosphamide is the most commonly used myeloablative pretransplantation conditioning therapy for myeloid leukemias. However, it is associated with significant nonrelapse mortality, which prohibits dose escalation to control relapse. We hypothesized that combining these two drugs with an epigenetic modifier would increase antileukemic efficacy without jeopardizing patient safety. Read More

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http://dx.doi.org/10.1016/j.exphem.2018.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262883PMC
November 2018
5 Reads
2.480 Impact Factor

Fluorescent genetic barcoding for cellular multiplex analyses.

Exp Hematol 2018 11 8;67:10-17. Epub 2018 Aug 8.

Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, Hannover, Germany; Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Hematopoiesis depends on the controlled differentiation of hematopoietic stem cells to mature cells with defined functions. Although each cell population within the hematopoietic hierarchy can be described by phenotypic markers, isolation of marker pure populations does not necessarily result in cells with homogeneous functionality. However, techniques that enable the efficient characterization of cell behavior with high resolution are limited. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0301472X183074
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http://dx.doi.org/10.1016/j.exphem.2018.08.001DOI Listing
November 2018
3 Reads