6,380 results match your criteria Experimental Hematology[Journal]


Acute Myeloid Leukemia Driven by the CALM-AF10 Fusion Gene is Dependent on BMI1.

Exp Hematol 2019 Apr 22. Epub 2019 Apr 22.

Tumor Initiation and Maintenance Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. Electronic address:

A subset of acute myeloid and lymphoid leukemia cases harbor a t(10;11)(p13;q14) translocation resulting in the CALM-AF10 fusion gene. Standard chemotherapeutic strategies are often ineffective in treating patients with CALM-AF10 fusions. Hence, there is an urgent need to identify molecular pathways dysregulated in CALM-AF10-positive leukemias which may lay the foundation for novel targeted therapies. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.04.003DOI Listing
April 2019
1 Read

Indirubin regulates MPL and TNF expression in peripheral blood mononuclear cells from patients with primary immune thrombocytopenia.

Exp Hematol 2019 Apr 20. Epub 2019 Apr 20.

Department of Hematology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan 250012, China.

Indirubin, a traditional Chinese medicine, is currently used to treat certain autoimmune diseases such as primary immune thrombocytopenia (ITP) in clinics. However, the effects of indirubin on related genes expression in peripheral blood mononuclear cells (PBMCs) from ITP patients have not been investigated. In the present study, PBMCs were isolated from 19 adult patients with well-characterized active ITP and 20 healthy controls (HCs) and were then treated with increasing concentrations of indirubin. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.04.002DOI Listing

Human Erythroblasts with c-Kit Activating Mutations Have Reduced Cell Culture Costs and Remain Capable of Terminal Maturation.

Exp Hematol 2019 Apr 17. Epub 2019 Apr 17.

Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester, Rochester, NY. Electronic address:

A major barrier to the in vitro production of red blood cells for transfusion therapy is the cost of culture components, with cytokines making up greater than half of the culture costs. Cell culture cytokines also represent a major expense for in vitro studies of human erythropoiesis. HUDEP2 cells are an E6/E7 immortalized erythroblast line used for the in vitro study of human erythropoiesis. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.04.001DOI Listing
April 2019
4 Reads

ETV6-RUNX1 interacts with a region in SPIB intron 1 to regulate gene expression in pre-B cell acute lymphoblastic leukemia.

Exp Hematol 2019 Apr 12. Epub 2019 Apr 12.

Department of Microbiology & Immunology and the Centre for Human Immunology, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada; Division of Genetics and Development, Children's Health Research Institute, Lawson Research Institute, London, Ontario, Canada. Electronic address:

The most frequently occurring genetic abnormality in pediatric B-ALL is the t(12;21) chromosomal translocation that results in a ETV6-RUNX1 (also known as TEL-AML1) fusion gene. Expression of ETV6-RUNX1 induces a preleukemic condition leading to acquisition of secondary driver mutations, but the mechanism is poorly understood. SPI-B (encoded by SPIB) is an important transcriptional activator of B cell development and differentiation. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.03.004DOI Listing
April 2019
1 Read
2.475 Impact Factor

The transcriptional regulators CITED2 and PU.1 cooperate in maintaining hematopoietic stem cells.

Exp Hematol 2019 Apr 12. Epub 2019 Apr 12.

Department of Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address:

Reduced expression of the transcription factor PU.1 is frequently associated with development of acute myeloid leukemia (AML), whereas elevated levels of CITED2 (CBP/p300-interacting-transactivator-with-an-ED-rich-tail 2) enhance maintenance of both normal and leukemic hematopoietic stem and progenitor cells (HSPCs). Recent findings indicated that PU. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.03.003DOI Listing
April 2019
2 Reads

Eltrombopag Promotes DNA Repair in Human Hematopoietic Stem and Progenitor Cells.

Exp Hematol 2019 Apr 12. Epub 2019 Apr 12.

National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NH), Bethesda, MD 20892, USA. Electronic address:

A causal link between hematopoietic stem/progenitor cell (HSPC) dysfunction and DNA damage accrual has been proposed. Clinically relevant strategies to maintain genome integrity in these cells are needed. Here we report that eltrombopag, a small molecule agonist of the thrombopoietin (TPO) receptor used in the clinic, promotes DNA double strand break (DSB) repair in human HSPCs. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.03.002DOI Listing
April 2019
2 Reads

KLF1 mutation E325K induces cell cycle arrest in erythroid cells differentiated from congenital dyserythropoietic anemia patient-specific induced pluripotent stem cells.

Exp Hematol 2019 Mar 12. Epub 2019 Mar 12.

Project Division of ALA Advanced Medical Research, The Institute of Medical Science, University of Tokyo, Tokyo, Japan; Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; Department of Advanced Molecular and Cell Therapy, Kyushu University Hospital, Fukuoka, Japan. Electronic address:

Krüppel-like factor 1 (KLF1), a transcription factor controlling definitive erythropoiesis, is involved in sequential control of terminal cell division and enucleation via fine regulation of key cell cycle regulator gene expression in erythroid lineage cells. Type IV congenital dyserythropoietic anemia (CDA) is caused by a monoallelic mutation at the second zinc finger of KLF1 (c.973G>A, p. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.03.001DOI Listing
March 2019
11 Reads

Difference in megakaryocyte expression of GATA-1, IL-6, and IL-8 associated with maintenance of platelet counts in patients with plasma cell neoplasm with dysmegakaryopoiesis.

Exp Hematol 2019 Feb 27. Epub 2019 Feb 27.

Department of Laboratory Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea. Electronic address:

Dysmegakaryopoiesis is a diagnostic criterion for myelodysplastic syndrome (MDS), which accompanies thrombocytopenia. Recently, dysmegakaryopoiesis was reported in patients with plasma cell neoplasm (PCN). Although these patients maintained normal platelet counts, disease progressed, with most bone marrow cells being replaced by plasma cells. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.02.005DOI Listing
February 2019
9 Reads

Activin A contributes to the definition of a pro-oncogenic bone marrow microenvironment in t(12;21) preleukemia.

Exp Hematol 2019 Feb 28. Epub 2019 Feb 28.

Centro Ricerca Tettamanti, Pediatric Department, University of Milano-Bicocca, Fondazione MBBM, Monza, Italy. Electronic address:

The TEL-AML1 fusion gene, generated by the t(12;21) chromosome translocation, arises in a progenitor/stem cell and could induce clonal expansion of a persistent preleukemic B-cell clone which, on acquisition of secondary alterations, may turn into full-blown leukemia. During infections, deregulated cytokine signaling, including transforming growth factor β (TGF-β), can further accelerate this process by creating a protumoral bone marrow (BM) microenvironment. Here, we show that activin A, a member of the TGF-β family induced under inflammatory conditions, inhibits the proliferation of normal progenitor B cells but not that of preleukemic TEL-AML1-positive clones, thereby providing a selective advantage to the latter. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.02.006DOI Listing
February 2019

DNA damage response-related alterations define the genetic background of patients with chronic lymphocytic leukemia and chromosomal gains.

Exp Hematol 2019 Apr 23;72:9-13. Epub 2019 Feb 23.

Servicio de Hematología, IBSAL, IBMCC, CIC Universidad de Salamanca-CSIC, Hospital Universitario, Salamanca, Spain; Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain. Electronic address:

The presence of chromosomal gains other than trisomy 12 suggesting a hyperdiploid karyotype is extremely rare in chronic lymphocytic leukemia (CLL) and is associated with a dismal prognosis. However, the genetic mechanisms and mutational background of these patients have not been fully explored. To improve our understanding of the genetic underpinnings of this subgroup of CLL, seven CLL patients with several chromosomal gains were sequenced using a next-generation sequencing (NGS)-targeted approach. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.02.003DOI Listing
April 2019
8 Reads

ATP produced by anaerobic glycolysis is essential for enucleation of human erythroblasts.

Exp Hematol 2019 Apr 22;72:14-26.e1. Epub 2019 Feb 22.

Department of Life Science, Graduate School of Engineering Science, Akita University, Akita, Japan; Research Center for Engineering Science, Graduate School of Engineering Science, Akita University, Akita, Japan.

More than 2million human erythroblasts extrude their nuclei every second in bone marrow under hypoxic conditions (<7% O). Enucleation requires specific signal transduction pathways and the local assembly of contractile actomyosin rings. However, the energy source driving these events has not yet been identified. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.02.004DOI Listing
April 2019
6 Reads

Introduction.

Exp Hematol 2019 03 12;71:1-2. Epub 2019 Feb 12.

British Columbia Cancer Research Centre, Vancouver, BC.

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http://dx.doi.org/10.1016/j.exphem.2019.02.001DOI Listing
March 2019
2 Reads

Vorinostat synergizes with antioxidant therapy to target myeloproliferative neoplasms.

Exp Hematol 2019 Apr 13;72:60-71.e11. Epub 2019 Feb 13.

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:

BCR-ABL-negative myeloproliferative neoplasms (MPNs) 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 MPNs but exhibit dose-limiting toxicity. The treatment of primary MPN cells with vorinostat modulates the expression of genes associated with apoptosis, cell cycle, inflammation, and signaling. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.02.002DOI Listing
April 2019
4 Reads

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

Exp Hematol 2019 Apr 26;72:27-35. 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
April 2019
1 Read

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

Exp Hematol 2019 Apr 26;72:72. 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

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

Exp Hematol 2019 03 19;71:32-42. 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
March 2019
13 Reads

Application of induced pluripotent stem cells to primary immunodeficiency diseases.

Exp Hematol 2019 03 19;71:43-50. 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
March 2019
6 Reads

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

Exp Hematol 2019 03 16;71:61-67. 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
March 2019
4 Reads

Induced pluripotent stem cell modeling of malignant hematopoiesis.

Exp Hematol 2019 03 16;71:68-76. 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
March 2019
3 Reads

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

Exp Hematol 2019 Apr 16;72:47-59.e1. 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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https://linkinghub.elsevier.com/retrieve/pii/S0301472X193001
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http://dx.doi.org/10.1016/j.exphem.2019.01.004DOI Listing
April 2019
9 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 Apr 9;72:1-8. 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
April 2019
63 Reads
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 03 4;71:51-60. 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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https://linkinghub.elsevier.com/retrieve/pii/S0301472X193000
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http://dx.doi.org/10.1016/j.exphem.2018.12.006DOI Listing
March 2019
6 Reads

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

Exp Hematol 2019 Apr 4;72:36-46. 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 are 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456912PMC
April 2019
6 Reads

Development of innate immune cells from human pluripotent stem cells.

Exp Hematol 2019 03 4;71:13-23. 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401218PMC
March 2019
1 Read

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

Exp Hematol 2019 02 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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https://linkinghub.elsevier.com/retrieve/pii/S0301472X183098
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http://dx.doi.org/10.1016/j.exphem.2018.12.002DOI Listing
February 2019
14 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 02 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
1 Read

From pluripotent stem cells to T cells.

Exp Hematol 2019 03 24;71:24-31. 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
March 2019
4 Reads

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

Exp Hematol 2019 02 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
7 Reads

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

Exp Hematol 2018 12 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
15 Reads

Smc3 is required for mouse embryonic and adult hematopoiesis.

Exp Hematol 2019 02 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
13 Reads

Arterial identity of hemogenic endothelium: a key to unlock definitive hematopoietic commitment in human pluripotent stem cell cultures.

Exp Hematol 2019 03 28;71:3-12. 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401300PMC
March 2019
5 Reads

Modeling myeloid malignancies with patient-derived iPSCs.

Exp Hematol 2019 03 24;71:77-84. 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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https://linkinghub.elsevier.com/retrieve/pii/S0301472X183092
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http://dx.doi.org/10.1016/j.exphem.2018.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401282PMC
March 2019
10 Reads

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

Exp Hematol 2018 12 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
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Message from the Editor.

Authors:
Connie Eaves

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

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December 2018
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The case for plerixafor to replace filgrastim as the optimal agent to mobilize peripheral blood donors for allogeneic hematopoietic cell transplantation.

Exp Hematol 2019 02 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
13 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 02 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
21 Reads

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

Exp Hematol 2019 02 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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http://dx.doi.org/10.1016/j.exphem.2018.11.002DOI Listing
February 2019
13 Reads

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

Exp Hematol 2019 02 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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http://dx.doi.org/10.1016/j.exphem.2018.11.001DOI Listing
February 2019
20 Reads

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

Exp Hematol 2018 12 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
13 Reads

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

Exp Hematol 2019 02 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
21 Reads

RUNX1 and the endothelial origin of blood.

Exp Hematol 2018 12 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
20 Reads
2.480 Impact Factor

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

Exp Hematol 2019 01 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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http://dx.doi.org/10.1016/j.exphem.2018.10.007DOI Listing
January 2019
5 Reads

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

Exp Hematol 2019 01 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
20 Reads

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

Exp Hematol 2019 01 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
24 Reads

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

Exp Hematol 2019 01 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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January 2019
2 Reads
2.480 Impact Factor

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

Exp Hematol 2019 01 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
13 Reads

TCF4 promotes erythroid development.

Exp Hematol 2019 01 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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http://dx.doi.org/10.1016/j.exphem.2018.10.002DOI Listing
January 2019
10 Reads

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

Exp Hematol 2019 01 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472707PMC
January 2019
4 Reads

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

Exp Hematol 2018 12 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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http://dx.doi.org/10.1016/j.exphem.2018.09.008DOI Listing
December 2018
27 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 12 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
16 Reads