11,481 results match your criteria Leukemia[Journal]


Monitoring tumour burden and therapeutic response through analysis of circulating tumour DNA and extracellular RNA in multiple myeloma patients.

Leukemia 2019 Apr 16. Epub 2019 Apr 16.

Myeloma Research Group, Australian Centre for Blood Diseases, Alfred Hospital-Monash University, Melbourne, VIC, Australia.

Monitoring tumour burden and therapeutic response through analyses of circulating cell-free tumour DNA (ctDNA) and extracellular RNA (exRNA) in multiple myeloma (MM) patients were performed in a Phase Ib trial of 24 relapsed/refractory patients receiving oral azacitidine in combination with lenalidomide and dexamethasone. Mutational characterisation of paired BM and PL samples at study entry identified that patients with a higher number of mutations or a higher mutational fractional abundance in PL had significantly shorter overall survival (OS) (p = 0.005 and p = 0. Read More

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http://dx.doi.org/10.1038/s41375-019-0469-xDOI Listing

Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells.

Leukemia 2019 Apr 15. Epub 2019 Apr 15.

Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA.

IL-6 signaling plays a crucial role in the pathogenesis of a number of diseases, including multiple myeloma, primary amyloidosis, cytokine release syndrome and other inflammatory conditions. It is central for the growth and survival of malignant plasma cells. IL-6R and IL-6ST receptors transduce IL-6 signaling. Read More

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http://dx.doi.org/10.1038/s41375-019-0470-4DOI Listing
April 2019
1 Read

Enasidenib, an inhibitor of mutant IDH2 proteins, induces durable remissions in older patients with newly diagnosed acute myeloid leukemia.

Leukemia 2019 Apr 9. Epub 2019 Apr 9.

Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Older adults with acute myeloid leukemia (AML) who are not fit for standard chemotherapy historically have poor outcomes. Approximately 12-15% of older patients with AML harbor isocitrate dehydrogenase 2 (IDH2) gene mutations. Enasidenib is an oral inhibitor of mutant IDH2 proteins. Read More

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http://www.nature.com/articles/s41375-019-0472-2
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http://dx.doi.org/10.1038/s41375-019-0472-2DOI Listing
April 2019
6 Reads
10.431 Impact Factor

SETD2 mutations confer chemoresistance in acute myeloid leukemia partly through altered cell cycle checkpoints.

Leukemia 2019 Apr 9. Epub 2019 Apr 9.

Divisions of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA.

SETD2, an epigenetic tumor suppressor, is frequently mutated in MLL-rearranged (MLLr) leukemia and relapsed acute leukemia (AL). To clarify the impact of SETD2 mutations on chemotherapy sensitivity in MLLr leukemia, two loss-of-function (LOF) Setd2-mutant alleles (Setd2 or Setd2) were generated and introduced, respectively, to the Mll-Af9 knock-in leukemia mouse model. Both alleles cooperated with Mll-Af9 to accelerate leukemia development that resulted in resistance to standard Cytarabine-based chemotherapy. Read More

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http://dx.doi.org/10.1038/s41375-019-0456-2DOI Listing

Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma.

Leukemia 2019 Apr 9. Epub 2019 Apr 9.

ProfilExpert, Lyon, France.

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http://dx.doi.org/10.1038/s41375-019-0452-6DOI Listing
April 2019
1 Read
10.431 Impact Factor

JAK2 p.G571S in B-cell precursor acute lymphoblastic leukemia: a synergizing germline susceptibility.

Leukemia 2019 Apr 9. Epub 2019 Apr 9.

Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich-Heine University Düsseldorf, Medical Faculty, Düsseldorf, Germany.

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http://dx.doi.org/10.1038/s41375-019-0459-zDOI Listing
April 2019
2 Reads

Transforming growth factor (TGF)-β pathway as a therapeutic target in lower risk myelodysplastic syndromes.

Leukemia 2019 Apr 8. Epub 2019 Apr 8.

Department of Internal Medicine, Section of Hematology, Yale University School of Medicine, New Haven, CT, USA.

The transforming growth factor (TGF)-β superfamily comprises more than 30 soluble growth factors that play a central role in erythropoiesis and are part of a tightly regulated myelosuppressive negative feedback loop under physiologic conditions. TGF-β receptor activation and phosphorylation trigger a regulatory circuit of activating and inhibitory SMAD proteins and increased activation of the TGF-β signaling pathway either by a loss of negative feedback or constitutive activation has been associated with the myelosuppression and ineffective erythropoiesis in myelodysplastic syndromes (MDS). Anemia is the predominant cause of morbidity and quality of life impairment in patients with lower-risk (LR)-MDS, and there are very limited therapy options for these patients after failure of erythropoiesis stimulating agents (ESAs). Read More

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http://dx.doi.org/10.1038/s41375-019-0448-2DOI Listing
April 2019
1 Read

The phosphatase UBASH3B/Sts-1 is a negative regulator of Bcr-Abl kinase activity and leukemogenesis.

Leukemia 2019 Apr 8. Epub 2019 Apr 8.

CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.

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http://dx.doi.org/10.1038/s41375-019-0468-yDOI Listing

Development and preclinical validation of a novel covalent ubiquitin receptor Rpn13 degrader in multiple myeloma.

Leukemia 2019 Apr 8. Epub 2019 Apr 8.

LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Proteasome inhibition is an effective treatment for multiple myeloma (MM); however, targeting different components of the ubiquitin-proteasome system (UPS) remains elusive. Our RNA-interference studies identified proteasome-associated ubiquitin-receptor Rpn13 as a mediator of MM cell growth and survival. Here, we developed the first degrader of Rpn13, WL40, using a small-molecule-induced targeted protein degradation strategy to selectively degrade this component of the UPS. Read More

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http://dx.doi.org/10.1038/s41375-019-0467-zDOI Listing
April 2019
10 Reads
10.431 Impact Factor

Identification of a leukemia-initiating stem cell in human mast cell leukemia.

Leukemia 2019 Apr 5. Epub 2019 Apr 5.

Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, 1090, Vienna, Austria.

Mast cell leukemia (MCL) is a highly fatal malignancy characterized by devastating expansion of immature mast cells in various organs. Although considered a stem cell disease, little is known about MCL-propagating neoplastic stem cells. We here describe that leukemic stem cells (LSCs) in MCL reside within a CD34/CD38 fraction of the clone. Read More

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http://dx.doi.org/10.1038/s41375-019-0460-6DOI Listing
April 2019
3 Reads

Prognostic and predictive value of a microRNA signature in adults with T-cell lymphoblastic lymphoma.

Leukemia 2019 Apr 5. Epub 2019 Apr 5.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4. Read More

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http://dx.doi.org/10.1038/s41375-019-0466-0DOI Listing
April 2019
1 Read
10.431 Impact Factor

The novel dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234 triggers differentiation and is effective in the treatment of myeloid malignancies.

Leukemia 2019 Apr 2. Epub 2019 Apr 2.

Bayer AG, Muellerstrasse 178, 13353, Berlin, Germany.

Acute myeloid leukemia (AML) is a devastating disease, with the majority of patients dying within a year of diagnosis. For patients with relapsed/refractory AML, the prognosis is particularly poor with currently available treatments. Although genetically heterogeneous, AML subtypes share a common differentiation arrest at hematopoietic progenitor stages. Read More

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http://dx.doi.org/10.1038/s41375-019-0461-5DOI Listing
April 2019
3 Reads

Clinical, histopathological and molecular characterization of hypoplastic myelodysplastic syndrome.

Leukemia 2019 Apr 2. Epub 2019 Apr 2.

Department of Haematological Medicine, King's College Hospital, London, UK.

Diagnostic criteria for hypoplastic myelodysplasic syndrome (h-MDS) have not been clearly established, making the differential diagnosis from other bone marrow failure syndromes (BMF) challenging. In this study, we aimed to delineate clinical, histopathological, and molecular features of h-MDS, based on a large and well-annotated cohort of patients with bone marrow (BM) hypocellularity. The study included 534 consecutive adult patients with hypocellular BM (278 h-MDS and 136 aplastic anemia), and 727 with normo- or hypercellular MDS (n-MDS). Read More

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http://dx.doi.org/10.1038/s41375-019-0457-1DOI Listing
April 2019
3 Reads

CSF1R and BTK inhibitions as novel strategies to disrupt the dialog between mantle cell lymphoma and macrophages.

Leukemia 2019 Apr 2. Epub 2019 Apr 2.

CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France.

The microenvironment strongly influences mantle cell lymphoma (MCL) survival, proliferation, and chemoresistance. However, little is known regarding the molecular characterization of lymphoma niches. Here, we focused on the interplay between MCL cells and the associated monocytes/macrophages. Read More

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http://dx.doi.org/10.1038/s41375-019-0463-3DOI Listing
April 2019
2 Reads

Blocking ATM-dependent NF-κB pathway overcomes niche protection and improves chemotherapy response in acute lymphoblastic leukemia.

Leukemia 2019 Apr 2. Epub 2019 Apr 2.

Key Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.

Bone marrow (BM) niche responds to chemotherapy-induced cytokines secreted from acute lymphoblastic leukemia (ALL) cells and protects the residual cells from chemotherapeutics in vivo. However, the underlying molecular mechanisms for the induction of cytokines by chemotherapy remain unknown. Here, we found that chemotherapeutic drugs (e. Read More

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http://dx.doi.org/10.1038/s41375-019-0458-0DOI Listing
April 2019
3 Reads
10.431 Impact Factor

Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis.

Leukemia 2019 Apr 1. Epub 2019 Apr 1.

Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.

The histone demethylase KDM6B (JMJD3) is upregulated in blood disorders, suggesting that it may have important pathogenic functions. Here we examined the function of Kdm6b in hematopoietic stem cells (HSC) to evaluate its potential as a therapeutic target. Loss of Kdm6b lead to depletion of phenotypic and functional HSCs in adult mice, and Kdm6b is necessary for HSC self-renewal in response to inflammatory and proliferative stress. Read More

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http://dx.doi.org/10.1038/s41375-019-0462-4DOI Listing
April 2019
4 Reads
10.431 Impact Factor

A distinct epigenetic program underlies the 1;7 translocation in myelodysplastic syndromes.

Leukemia 2019 Mar 28. Epub 2019 Mar 28.

Department of Medicine, Hematology and Bone Marrow Transplantation Unit, University of Perugia, Perugia, Italy.

The unbalanced translocation dic(1;7)(q10;p10) in myelodysplastic syndromes (MDS) is originated by centromeric juxtaposition resulting into 1q trisomy and 7q monosomy. More than half of cases arise after chemo/radio-therapy. To date, given the absence of genes within the centromeric regions, no specific molecular events have been identified in this cytogenetic subgroup. Read More

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http://www.nature.com/articles/s41375-019-0433-9
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http://dx.doi.org/10.1038/s41375-019-0433-9DOI Listing
March 2019
4 Reads

Quality of life and mood of older patients with acute myeloid leukemia (AML) receiving intensive and non-intensive chemotherapy.

Leukemia 2019 Mar 28. Epub 2019 Mar 28.

Massachusetts General Hospital, Boston, MA, USA.

Older patients with AML face difficult treatment decisions as they can be treated either with 'intensive' chemotherapy requiring prolonged hospitalization, or 'non-intensive' chemotherapy. Although clinicians often perceive intensive chemotherapy as more burdensome, research is lacking on patients' quality of life (QOL) and psychological distress. We conducted a longitudinal study of older patients (≥60 years) newly diagnosed with AML receiving intensive (cytarabine/anthracycline combination) or non-intensive (hypomethylating agents) chemotherapy. Read More

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http://www.nature.com/articles/s41375-019-0449-1
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http://dx.doi.org/10.1038/s41375-019-0449-1DOI Listing
March 2019
3 Reads

Transient stabilization, rather than inhibition, of MYC amplifies extrinsic apoptosis and therapeutic responses in refractory B-cell lymphoma.

Leukemia 2019 Mar 26. Epub 2019 Mar 26.

Division of Cancer Pathobiology, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.

Therapeutic targeting of initiating oncogenes is the mainstay of precision medicine. Considerable efforts have been expended toward silencing MYC, which drives many human cancers including Burkitt lymphomas (BL). Yet, the effects of MYC silencing on standard-of-care therapies are poorly understood. Read More

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http://dx.doi.org/10.1038/s41375-019-0454-4DOI Listing
March 2019
2 Reads

Short telomeres are associated with inferior outcome, genomic complexity, and clonal evolution in chronic lymphocytic leukemia.

Leukemia 2019 Mar 25. Epub 2019 Mar 25.

Department of Internal Medicine III, Ulm University, Ulm, Germany.

Telomere length in chronic lymphocytic leukemia (CLL) has been shown to be of prognostic importance, but the analyses have largely been executed on heterogeneous patient cohorts outside of clinical trials. In the present study, we performed a comprehensive analysis of telomere length associations in the well characterized CLL8 trial (n = 620) of the German CLL study group, with validation in a representative cohort of the CLL4 trial (n = 293). Absolute telomere length was analyzed using quantitative-PCR. Read More

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http://www.nature.com/articles/s41375-019-0446-4
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http://dx.doi.org/10.1038/s41375-019-0446-4DOI Listing
March 2019
2 Reads

Inhibitory effects of midostaurin and avapritinib on myeloid progenitors derived from patients with KIT D816V positive advanced systemic mastocytosis.

Leukemia 2019 Mar 25. Epub 2019 Mar 25.

Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.

Advanced systemic mastocytosis (advSM) is characterized by the presence of an acquired KIT D816V mutation in >90% of patients. In the majority of patients, KIT D816V is not only detected in mast cells but also in other hematopoietic lineages. We sought to investigate the effects of the KIT-inhibitors midostaurin and avapritinib on single-cell-derived myeloid progenitor cells using granulocyte-macrophage colony-forming-units of patients with KIT D816V positive advSM. Read More

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http://www.nature.com/articles/s41375-019-0450-8
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http://dx.doi.org/10.1038/s41375-019-0450-8DOI Listing
March 2019
3 Reads

Correction: Genomic profiling reveals spatial intra-tumor heterogeneity in follicular lymphoma.

Leukemia 2019 Mar 23. Epub 2019 Mar 23.

Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.

In the original version of this article the authors noted an omission in the author affiliations where the university details: Queen Mary University of London was not included in the original affiliation for the majority of the authors. The correct affiliations are as follows1. Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK3. Read More

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http://dx.doi.org/10.1038/s41375-019-0425-9DOI Listing
March 2019
1 Read

Insertional mutagenesis identifies cooperation between Setbp1 and Mllt3 in inducing myeloid leukemia development.

Leukemia 2019 Mar 20. Epub 2019 Mar 20.

Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

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http://dx.doi.org/10.1038/s41375-019-0445-5DOI Listing

Biology and prognostic impact of clonal plasmacytoid dendritic cells in chronic myelomonocytic leukemia.

Leukemia 2019 Mar 20. Epub 2019 Mar 20.

INSERM U1170, Gustave Roussy Cancer Center, Villejuif, France.

Islands of CD123 cells have been commonly described in the bone marrow of patients with chronic myelomonocytic leukemia (CMML). Using a multiparameter flow cytometry assay, we detected an excess of CD123 mononucleated cells that are lineage-negative, CD45, CD11c, CD33, HLA-DR, BDCA-2, BDCA-4 in the bone marrow of 32/159 (20%) patients. Conventional and electron microscopy, flow cytometry detection of cell surface markers, gene expression analyses, and the ability to synthesize interferon alpha in response to Toll-like receptor agonists identified these cells as bona fide plasmacytoid dendritic cells (pDCs). Read More

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http://dx.doi.org/10.1038/s41375-019-0447-3DOI Listing

CD8 T cells expand stem and progenitor cells in favorable but not adverse risk acute myeloid leukemia.

Leukemia 2019 Mar 15. Epub 2019 Mar 15.

Tumor Immunology, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.

CD8 T cell immunosurveillance is crucial in solid tumors and T cell dysfunction leads to tumor progression. In contrast, the role of CD8 T cells in the control of leukemia is less clear. We characterized the molecular signature of leukemia stem/progenitor cells (LSPCs) and paired CD8 T cells in patients with acute myeloid leukemia (AML). Read More

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http://dx.doi.org/10.1038/s41375-019-0441-9DOI Listing
March 2019
2 Reads

Skeletal muscle toxicity associated with tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia.

Leukemia 2019 Mar 14. Epub 2019 Mar 14.

Radboud Institute for Health Sciences, Department of Physiology, Radboud University Medical Center, Nijmegen, The Netherlands.

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http://dx.doi.org/10.1038/s41375-019-0443-7DOI Listing
March 2019
1 Read

Inhibition of SYK or BTK augments venetoclax sensitivity in SHP1-negative/BCL-2-positive diffuse large B-cell lymphoma.

Leukemia 2019 Mar 14. Epub 2019 Mar 14.

Molecular Hematology, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.

The BCL-2 inhibitor venetoclax has only limited activity in DLBCL despite frequent BCL-2 overexpression. Since constitutive activation of the B cell receptor (BCR) pathway has been reported in both ABC and GCB DLBCL, we investigated whether targeting SYK or BTK will increase sensitivity of DLBCL cells to venetoclax. We report that pharmacological inhibition of SYK or BTK synergistically enhances venetoclax sensitivity in BCL-2-positive DLBCL cell lines with an activated BCR pathway in vitro and in a xenograft model in vivo, despite the only modest direct cytotoxic effect. Read More

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http://dx.doi.org/10.1038/s41375-019-0442-8DOI Listing
March 2019
2 Reads

Selective targeting of multiple myeloma by B cell maturation antigen (BCMA)-specific central memory CD8 cytotoxic T lymphocytes: immunotherapeutic application in vaccination and adoptive immunotherapy.

Leukemia 2019 Mar 12. Epub 2019 Mar 12.

Dana-Farber Cancer Institute, Boston, MA, USA.

To expand the breadth and extent of current multiple myeloma (MM)-specific immunotherapy, we have identified various antigens on CD138 tumor cells from newly diagnosed MM patients (n = 616) and confirmed B-cell maturation antigen (BCMA) as a key myeloma-associated antigen. The aim of this study is to target the BCMA, which promotes MM cell growth and survival, by generating BCMA-specific memory CD8 CTL that mediate effective and long-lasting immunity against MM. Here we report the identification of novel engineered peptides specific to BCMA, BCMA (YLMFLLRKI), and BCMA (YILWTCLGL), which display improved affinity/stability to HLA-A2 compared to their native peptides and induce highly functional BCMA-specific CTL with increased activation (CD38, CD69) and co-stimulatory (CD40L, OX40, GITR) molecule expression. Read More

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http://dx.doi.org/10.1038/s41375-019-0414-zDOI Listing
March 2019
4 Reads

Chromatin remodeling mediated by ARID1A is indispensable for normal hematopoiesis in mice.

Leukemia 2019 Mar 11. Epub 2019 Mar 11.

Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.

Precise regulation of chromatin architecture is vital to physiological processes including hematopoiesis. ARID1A is a core component of the mammalian SWI/SNF complex, which is one of the ATP-dependent chromatin remodeling complexes. To uncover the role of ARID1A in hematopoietic development, we utilized hematopoietic cell-specific deletion of Arid1a in mice. Read More

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http://dx.doi.org/10.1038/s41375-019-0438-4DOI Listing

Degradation of Bruton's tyrosine kinase mutants by PROTACs for potential treatment of ibrutinib-resistant non-Hodgkin lymphomas.

Leukemia 2019 Mar 11. Epub 2019 Mar 11.

MOE Key Laboratory of Protein Sciences, School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing, 100084, P.R. China.

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http://dx.doi.org/10.1038/s41375-019-0440-xDOI Listing
March 2019
1 Read

Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1.

Leukemia 2019 Mar 11. Epub 2019 Mar 11.

School of Medicine, Division of Cancer and Hematology, Cardiff University, Cardiff, UK.

Minimal residual disease (MRD) is a powerful prognostic factor in acute lymphoblastic leukemia (ALL) and is used for patient stratification and treatment decisions, but its precise role in Philadelphia chromosome positive ALL is less clear. This uncertainty results largely from methodological differences relating to the use of real-time quantitative PCR (qRT-PCR) to measure BCR-ABL1 transcript levels for MRD analysis. We here describe the first results by the EURO-MRD consortium on standardization of qRT-PCR for the e1a2 BCR-ABL1 transcript in Ph + ALL, designed to overcome the lack of standardisation of laboratory procedures and data interpretation. Read More

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http://dx.doi.org/10.1038/s41375-019-0413-0DOI Listing
March 2019
1 Read

Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy.

Leukemia 2019 Mar 11. Epub 2019 Mar 11.

Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.

The introduction of CD38-targeting monoclonal antibodies (CD38 MoABs), daratumumab and isatuximab, has significantly impacted the management of patients with multiple myeloma (MM). Outcomes of patients with MM refractory to CD38 MoABs have not been described. We analyzed outcomes of 275 MM patients at 14 academic centers with disease refractory to CD38 MoABs. Read More

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http://dx.doi.org/10.1038/s41375-019-0435-7DOI Listing
March 2019
1 Read

Expression and functional relevance of long non-coding RNAs in acute myeloid leukemia stem cells.

Leukemia 2019 Mar 11. Epub 2019 Mar 11.

The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.

In acute myeloid leukemia (AML), novel therapies are needed to target not only the rapidly dividing AML blasts but also the distinct population of leukemia stem cells (LSCs), which have abnormal self-renewal capacity and increased chemotherapy resistance. Elucidation of the expression and function of deregulated genes in LSCs is critical to specifically target LSCs and may consequently lead to improving outcomes of AML patients. Here, we correlated long non-coding RNA (lncRNA) expression profiles obtained from two RNA-seq datasets of 375 younger (aged <60 years) 76 older (≥60 years) adults with cytogenetically normal AML with a 'core enriched' (CE) gene expression signature (GES) associated with LSCs. Read More

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http://dx.doi.org/10.1038/s41375-019-0429-5DOI Listing
March 2019
1 Read

A fully human anti-IL-7Rα antibody promotes antitumor activity against T-cell acute lymphoblastic leukemia.

Leukemia 2019 Mar 8. Epub 2019 Mar 8.

Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer for which treatment options often result in incomplete therapeutic efficacy and long-term side-effects. Interleukin 7 (IL-7) and its receptor IL-7Rα promote T-ALL development and mutational activation of IL-7Rα associates with very high risk in relapsed disease. Using combinatorial phage-display libraries and antibody reformatting, we generated a fully human IgG1 monoclonal antibody (named B12) against both wild-type and mutant human IL-7Rα, predicted to form a stable complex with IL-7Rα at a different site from IL-7. Read More

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http://dx.doi.org/10.1038/s41375-019-0434-8DOI Listing
March 2019
2 Reads

Correction: The ribosomal RPL10 R98S mutation drives IRES-dependent BCL-2 translation in T-ALL.

Leukemia 2019 Apr;33(4):1055-1062

Department of Oncology, Laboratory for Disease Mechanisms in Cancer, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium.

Following the publication of this article, the authors noted that Dr Laura Fancello was not listed among the authors. The corrected author list is given below. Additionally, the following was not included in the author contribution statement: 'L. Read More

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http://dx.doi.org/10.1038/s41375-019-0424-xDOI Listing

NLRP3 inflammasome couples purinergic signaling with activation of the complement cascade for the optimal release of cells from bone marrow.

Leukemia 2019 Apr 7;33(4):815-825. Epub 2019 Mar 7.

Center for Preclinical Studies and Technology, Department of Regenerative Medicine Warsaw Medical University, Warsaw, Poland.

The mechanisms that regulate egress of hematopoietic stem/progenitor cells (HSPCs) into peripheral blood (PB) in response to stress, inflammation, tissue/organ injury, or administration of mobilization-inducing drugs are still not well understood, and because of the importance of stem cell trafficking in maintaining organism homeostasis, several complementary pathways are believed to be involved. Our group proposes that mobilization of HSPCs is mainly a result of sterile inflammation in the bone marrow (BM) microenvironment in response to pro-mobilizing stimuli and that during the initiation phase of the mobilization process BM-residing cells belonging to the innate immunity system, including granulocytes and monocytes, release danger-associated molecular pattern molecules (DAMPs, also known as alarmins), reactive oxygen species (ROS), as well as proteolytic and lipolytic enzymes. These factors together orchestrate the release of HSPCs into PB. Read More

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http://dx.doi.org/10.1038/s41375-019-0436-6DOI Listing

Correction: Novel evidence that extracellular nucleotides and purinergic signaling induce innate immunity-mediated mobilization of hematopoietic stem/progenitor cells.

Leukemia 2019 Apr;33(4):1057

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.

Following the publication of this article, the authors noted that the following should be included in the Acknowledgements section: "MA is the recipient of a START scholarship (0785) from FNP". The authors wish to apologise for any inconvenience caused. Read More

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http://dx.doi.org/10.1038/s41375-019-0407-yDOI Listing

Prognostic significance of recurring chromosomal abnormalities in transplanted patients with acute myeloid leukemia.

Leukemia 2019 Mar 7. Epub 2019 Mar 7.

Hematology Division, Chaim Sheba Medical Center, Tel Aviv University, Tel-Hashomer, Israel.

Baseline cytogenetic studies at diagnosis remain the single most important determinant of outcome in patients with acute myeloid leukemia (AML). However, the prognostic role of the complete gamut of cytogenetic aberrations in AML patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently undefined. In addition, their significance in conjunction with FLT3-ITD status has not been addressed thus far. Read More

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http://dx.doi.org/10.1038/s41375-019-0439-3DOI Listing
March 2019
1 Read

PAX5 biallelic genomic alterations define a novel subgroup of B-cell precursor acute lymphoblastic leukemia.

Leukemia 2019 Mar 6. Epub 2019 Mar 6.

Department of Hematology/Oncology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.

Chromosomal rearrangements and specific aneuploidy patterns are initiating events and define subgroups in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Here we analyzed 250 BCP-ALL cases and identified a novel subgroup ('PAX5-plus', n = 19) by distinct DNA methylation and gene expression profiles. All patients in this subgroup harbored mutations in the B-lineage transcription factor PAX5, with p. Read More

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http://dx.doi.org/10.1038/s41375-019-0430-zDOI Listing
March 2019
2 Reads

Stem cell persistence in CML is mediated by extrinsically activated JAK1-STAT3 signaling.

Leukemia 2019 Mar 6. Epub 2019 Mar 6.

Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.

Tyrosine kinase inhibitor (TKI) therapy effectively blocks oncogenic Bcr-Abl signaling and induces molecular remission in the majority of CML patients. However, the disease-driving stem cell population is not fully targeted by TKI therapy in the majority of patients, and leukemic stem cells (LSCs) capable of re-inducing the disease can persist. In TKI-resistant CML, STAT3 inhibition was previously shown to reduce malignant cell survival. Read More

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http://www.nature.com/articles/s41375-019-0427-7
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http://dx.doi.org/10.1038/s41375-019-0427-7DOI Listing
March 2019
10 Reads

Response to the Commentary on "Is posttransplant lenalidomide the standard-of-care after an autotransplant for plasma cell myeloma".

Leukemia 2019 Mar 6. Epub 2019 Mar 6.

Haematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College, London, London, UK.

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http://dx.doi.org/10.1038/s41375-019-0432-xDOI Listing

Correction: Cancer from the perspective of stem cells and misappropriated tissue regeneration mechanisms.

Leukemia 2019 Apr;33(4):1058

Stem Cell Institute, Division of Hematology and Oncology, James Graham Brown Cancer Center, University Louisville, 500 South Floyd Street, Louisville, 40202, Kentucky, USA.

The original version of this Article omitted the following from the Acknowledgements. Read More

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http://dx.doi.org/10.1038/s41375-019-0411-2DOI Listing

Correction: Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia.

Leukemia 2019 Apr;33(4):1061-1062

Childrens Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.

We thank the research coordinators and following physicians at pediatric cancer centers for contributing data to this project: Prashant Hiwarkar and Jayashree Motwani, Birmingham Women's and Children's Hospital, UK; Kelly Malone, Children's Hospital of Colorado, USA; Mylene Bassal, Children's Hospital of Eastern Ontario, Canada; Yoav Messinger and Joanna Perkins, Children's Hospital of Minnesota, USA; Van Huynh, Children's Hospital of Orange County, USA; Richard Ho, Children's Hospital at Vanderbilt, USA; Joanne Chuah and Jessa Morales, Children's Hospital at Westmead, Australia; Donald Wells, Dell Children's Hospital, USA; Nicolas Boissel, Hospital Saint-Louis, France; Tannie Huang, Kaiser Permanente, USA; Stacey Marjerrison, McMaster Children's Hospital, Canada; William Carroll and Joanna Pierro, New York University Langone Medical Center, USA; Ajay Vora, Sheffield Children's Hospital, UK; Donna Lancaster, The Royal Marsden Hospital, UK; Lucie Šrámková, University Hospital Motol, Czech Republic; Chatchawin Assanasen, University of Texas Health Science Center, San Antonio, USA; Rupert Handgretinger, University of Tübingen, Germany. Read More

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http://dx.doi.org/10.1038/s41375-019-0426-8DOI Listing
April 2019
2 Reads