3,209 results match your criteria Clinical Leukemia [Journal]


Randomized phase-II trial evaluating induction therapy with idarubicin and etoposide plus sequential or concurrent azacitidine and maintenance therapy with azacitidine.

Leukemia 2019 Feb 6. Epub 2019 Feb 6.

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

The aim of this randomized phase-II study was to evaluate the effect of substituting cytarabine by azacitidine in intensive induction therapy of patients with acute myeloid leukemia (AML). Patients were randomized to four induction schedules for two cycles: STANDARD (idarubicin, cytarabine, etoposide); and azacitidine given prior (PRIOR), concurrently (CONCURRENT), or after (AFTER) therapy with idarubicin and etoposide. Consolidation therapy consisted of allogeneic hematopoietic-cell transplantation or three courses of high-dose cytarabine followed by 2-year maintenance therapy with azacitidine in the azacitidine-arms. Read More

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http://dx.doi.org/10.1038/s41375-019-0395-yDOI Listing
February 2019
2 Reads

Cytokine production in myelofibrosis exhibits differential responsiveness to JAK-STAT, MAP kinase, and NFκB signaling.

Leukemia 2019 Feb 4. Epub 2019 Feb 4.

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

The distinct clinical features of myelofibrosis (MF) have been attributed in part to dysregulated inflammatory cytokine production. Circulating cytokine levels are elevated in MF patients; a subset of which have been shown to be poor prognostic indicators. In this study, cytokine overproduction was examined in MF patient plasma and in MF blood cells ex vivo using mass cytometry. Read More

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http://www.nature.com/articles/s41375-019-0379-y
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http://dx.doi.org/10.1038/s41375-019-0379-yDOI Listing
February 2019
1 Read

Mesenchymal stem cells in suppression or progression of hematologic malignancy: current status and challenges.

Leukemia 2019 Jan 31. Epub 2019 Jan 31.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Mesenchymal stem cells (MSCs) are known for being multi-potent. However, they also possess anticancer properties, which has prompted efforts to adapt MSCs for anticancer therapies. However, MSCs have also been widely implicated in pathways that contribute to tumor growth. Read More

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http://dx.doi.org/10.1038/s41375-018-0373-9DOI Listing
January 2019

Telomere length predicts for outcome to FCR chemotherapy in CLL.

Leukemia 2019 Jan 30. Epub 2019 Jan 30.

Division of Cancer & Genetics, Cardiff University, School of Medicine, Heath Park, Cardiff, UK.

We have previously shown that dividing patients with CLL into those with telomeres inside the fusogenic range (TL-IFR) and outside the fusogenic range (TL-OFR) is powerful prognostic tool. Here, we used a high-throughput version of the assay (HT-STELA) to establish whether telomere length could predict for outcome to fludarabine, cyclophosphamide, rituximab (FCR)-based treatment using samples collected from two concurrent phase II studies, ARCTIC and ADMIRE (n = 260). In univariate analysis, patients with TL-IFR had reduced progression-free survival (PFS) (P < 0. Read More

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http://www.nature.com/articles/s41375-019-0389-9
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http://dx.doi.org/10.1038/s41375-019-0389-9DOI Listing
January 2019
3 Reads

Infections associated with immunotherapeutic and molecular targeted agents in hematology and oncology. A position paper by the European Conference on Infections in Leukemia (ECIL).

Leukemia 2019 Jan 30. Epub 2019 Jan 30.

Department of Hematology, University Hospitals Leuven, Leuven, Belgium.

A multitude of new agents for the treatment of hematologic malignancies has been introduced over the past decade. Hematologists, infectious disease specialists, stem cell transplant experts, pulmonologists and radiologists have met within the framework of the European Conference on Infections in Leukemia (ECIL) to provide a critical state-of-the-art on infectious complications associated with immunotherapeutic and molecular targeted agents used in clinical routine. For brentuximab vedotin, blinatumomab, CTLA4- and PD-1/PD-L1-inhibitors as well as for ibrutinib, idelalisib, HDAC inhibitors, mTOR inhibitors, ruxolitinib, and venetoclax, a detailed review of data available until August 2018 has been conducted, and specific recommendations for prophylaxis, diagnostic and differential diagnostic procedures as well as for clinical management have been developed. Read More

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http://dx.doi.org/10.1038/s41375-019-0388-xDOI Listing
January 2019

Rethinking clinical trial endpoints in myelodysplastic syndromes.

Leukemia 2019 Jan 30. Epub 2019 Jan 30.

Leukemia Programs, Cleveland Clinic Taussig Cancer Institute and Dana-Farber Cancer Institute, Cleveland, OH, and Boston, MA, USA.

The myelodysplastic syndromes (MDS) are a heterogeneous collection of clonal, hematopoietic disorders primarily affecting an older population, making successful drug development a complicated process. A sole focus on response rate in clinical trials is likely not clinically meaningful if not accompanied by substantive response duration, improvement in quality of life, and ideally prolongation of survival. The process of receiving a new therapy should not be more burdensome than the MDS sequela it is intended to ameliorate. Read More

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http://dx.doi.org/10.1038/s41375-018-0367-7DOI Listing
January 2019
2 Reads

The NUP98-HOXD13 fusion oncogene induces thymocyte self-renewal via Lmo2/Lyl1.

Leukemia 2019 Jan 30. Epub 2019 Jan 30.

Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia.

T cell acute lymphoblastic leukaemia (T-ALL) cases include subfamilies that overexpress the TAL1/LMO, TLX1/3 and HOXA transcription factor oncogenes. While it has been shown that TAL1/LMO transcription factors induce self-renewal of thymocytes, whether this is true for other transcription factor oncogenes is unknown. To address this, we have studied NUP98-HOXD13-transgenic (NHD13-Tg) mice, which overexpress HOXA transcription factors throughout haematopoiesis and develop both myelodysplastic syndrome (MDS) progressing to acute myeloid leukaemia (AML) as well as T-ALL. Read More

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http://www.nature.com/articles/s41375-018-0361-0
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http://dx.doi.org/10.1038/s41375-018-0361-0DOI Listing
January 2019
5 Reads

Ibrutinib reprograms the glucocorticoid receptor in chronic lymphocytic leukemia cells.

Leukemia 2019 Jan 29. Epub 2019 Jan 29.

Biology Platform, Sunnybrook Research Institute, M4N 3M5, Toronto, ON, Canada.

Glucocorticoid (GC) receptor (GR) phosphorylation and signature genes were studied in chronic lymphocytic leukemia (CLL) cells to help place GCs within modern treatment algorithms. In contrast to normal B and T cells, transcription of GC-regulated genes was not rhythmic and the synthetic GC dexamethasone (DEX) could not inhibit toll-like receptor (TLR)-responses in CLL cells. This intrinsic GC-resistance was associated with aberrant GR-phosphorylation on activating Ser211 and inhibitory Ser226 sites. Read More

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http://www.nature.com/articles/s41375-019-0381-4
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http://dx.doi.org/10.1038/s41375-019-0381-4DOI Listing
January 2019
2 Reads

European recommendations and quality assurance for cytogenomic analysis of haematological neoplasms.

Leukemia 2019 Jan 29. Epub 2019 Jan 29.

GenQA, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK.

Cytogenomic investigations of haematological neoplasms, including chromosome banding analysis, fluorescence in situ hybridisation (FISH) and microarray analyses have become increasingly important in the clinical management of patients with haematological neoplasms. The widespread implementation of these techniques in genetic diagnostics has highlighted the need for guidance on the essential criteria to follow when providing cytogenomic testing, regardless of choice of methodology. These recommendations provide an updated, practical and easily available document that will assist laboratories in the choice of testing and methodology enabling them to operate within acceptable standards and maintain a quality service. Read More

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http://dx.doi.org/10.1038/s41375-019-0378-zDOI Listing
January 2019

Is lenalidomide the standard-of-care after an autotransplant for plasma cell myeloma?

Leukemia 2019 Jan 28. Epub 2019 Jan 28.

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

Three randomized controlled trials and a meta-analysis reported lenalidomide given after high-dose therapy and an autologous hemopoietic cell transplantation is associated with increase in progression-free survival (PFS) and survival in persons with plasma cell myeloma (PCM). Based on these data, posttransplant lenalidomide is considered by many a standard-of-care in this setting. However, decisions on the use of new therapies should consider not only results of such trials and meta-analyses but also other factors including quality-of-evidence, anticipated desired and undesired effects of the drug, costs and feasibility of the therapy option. Read More

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http://www.nature.com/articles/s41375-019-0383-2
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http://dx.doi.org/10.1038/s41375-019-0383-2DOI Listing
January 2019
4 Reads

Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas.

Leukemia 2019 Jan 25. Epub 2019 Jan 25.

Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Viral infection induces potent cellular immunity and activated intracellular signaling, which may dictate the driver events involved in immune escape and clonal selection of virus-associated cancers, including Epstein-Barr virus (EBV)-positive lymphomas. Here, we thoroughly interrogated PD-L1/PD-L2-involving somatic aberrations in 384 samples from various lymphoma subtypes using high-throughput sequencing, particularly focusing on virus-associated lymphomas. A high frequency of PD-L1/PD-L2-involving genetic aberrations was observed in EBV-positive lymphomas [33 (22%) of 148 cases], including extranodal NK/T-cell lymphoma (ENKTL, 23%), aggressive NK-cell leukemia (57%), systemic EBV-positive T-cell lymphoproliferative disorder (17%) as well as EBV-positive diffuse large B-cell lymphoma (DLBCL, 19%) and peripheral T-cell lymphoma-not otherwise specified (15%). Read More

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http://dx.doi.org/10.1038/s41375-019-0380-5DOI Listing
January 2019
2 Reads

The future of myeloma precision medicine: integrating the compendium of known drug resistance mechanisms with emerging tumor profiling technologies.

Leukemia 2019 Jan 25. Epub 2019 Jan 25.

Department of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, MN, USA.

Multiple myeloma (MM) is a hematologic malignancy that is considered mostly incurable in large part due to the inability of standard of care therapies to overcome refractory disease and inevitable drug-resistant relapse. The post-genomic era has been a productive period of discovery where modern sequencing methods have been applied to large MM patient cohorts to modernize our current perception of myeloma pathobiology and establish an appreciation for the vast heterogeneity that exists between and within MM patients. Numerous pre-clinical studies conducted in the last two decades have unveiled a compendium of mechanisms by which malignant plasma cells can escape standard therapies, many of which have potentially quantifiable biomarkers. Read More

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http://dx.doi.org/10.1038/s41375-018-0362-zDOI Listing
January 2019
1 Read

Functional profiling of venetoclax sensitivity can predict clinical response in multiple myeloma.

Leukemia 2019 Jan 24. Epub 2019 Jan 24.

Department of Hematology and Medical Oncology, Emory University School of Medicine and the Winship Cancer Institute of Emory University, Atlanta, GA, USA.

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http://dx.doi.org/10.1038/s41375-018-0374-8DOI Listing
January 2019
1 Read

LSD1 inhibition by tranylcypromine derivatives interferes with GFI1-mediated repression of PU.1 target genes and induces differentiation in AML.

Leukemia 2019 Jan 24. Epub 2019 Jan 24.

Department of Medicine II, Hematology/Oncology, Goethe University, Frankfurt/Main, Germany.

LSD1 has emerged as a promising epigenetic target in the treatment of acute myeloid leukemia (AML). We used two murine AML models based on retroviral overexpression of Hoxa9/Meis1 (H9M) or MN1 to study LSD1 loss of function in AML. The conditional knockout of Lsd1 resulted in differentiation with both granulocytic and monocytic features and increased ATRA sensitivity and extended the survival of mice with H9M-driven AML. Read More

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http://dx.doi.org/10.1038/s41375-018-0375-7DOI Listing
January 2019
2 Reads

Twins with different personalities: STAT5B-but not STAT5A-has a key role in BCR/ABL-induced leukemia.

Leukemia 2019 Jan 24. Epub 2019 Jan 24.

Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, 1210, Vienna, Austria.

Deregulation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway is found in cancer with STAT5A/B controlling leukemic cell survival and disease progression. As mutations in STAT5B, but not STAT5A, have been frequently described in hematopoietic tumors, we used BCR/ABL as model systems to investigate the contribution of STAT5A or STAT5B for leukemogenesis. The absence of STAT5A decreased cell survival and colony formation. Read More

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http://www.nature.com/articles/s41375-018-0369-5
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http://dx.doi.org/10.1038/s41375-018-0369-5DOI Listing
January 2019
5 Reads

New study-designs to address the clinical complexity of acute myeloid leukemia.

Leukemia 2019 Jan 22. Epub 2019 Jan 22.

R. P. Gale - Haematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, UK.

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http://www.nature.com/articles/s41375-018-0363-y
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http://dx.doi.org/10.1038/s41375-018-0363-yDOI Listing
January 2019
3 Reads

Overexpression of CD49d in trisomy 12 chronic lymphocytic leukemia patients is mediated by IRF4 through induction of IKAROS.

Leukemia 2019 Jan 18. Epub 2019 Jan 18.

Hematology Unit, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.

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http://dx.doi.org/10.1038/s41375-018-0296-5DOI Listing
January 2019
1 Read

Targeting FLT3 mutations in AML: review of current knowledge and evidence.

Leukemia 2019 Feb 16;33(2):299-312. Epub 2019 Jan 16.

Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.

Genomic investigations of acute myeloid leukemia (AML) have demonstrated that several genes are recurrently mutated, leading to new genomic classifications, predictive biomarkers, and new therapeutic targets. Mutations of the FMS-like tyrosine kinase 3 (FLT3) gene occur in approximately 30% of all AML cases, with the internal tandem duplication (ITD) representing the most common type of FLT3 mutation (FLT3-ITD; approximately 25% of all AML cases). FLT3-ITD is a common driver mutation that presents with a high leukemic burden and confers a poor prognosis in patients with AML. Read More

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http://www.nature.com/articles/s41375-018-0357-9
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http://dx.doi.org/10.1038/s41375-018-0357-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365380PMC
February 2019
17 Reads

Rps14, Csnk1a1 and miRNA145/miRNA146a deficiency cooperate in the clinical phenotype and activation of the innate immune system in the 5q- syndrome.

Leukemia 2019 Jan 16. Epub 2019 Jan 16.

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

RPS14, CSNK1A1, and miR-145 are universally co-deleted in the 5q- syndrome, but mouse models of each gene deficiency recapitulate only a subset of the composite clinical features. We analyzed the combinatorial effect of haploinsufficiency for Rps14, Csnk1a1, and miRNA-145, using mice with genetically engineered, conditional heterozygous inactivation of Rps14 and Csnk1a1 and stable knockdown of miR-145/miR-146a. Combined Rps14/Csnk1a1/miR-145/146a deficiency recapitulated the cardinal features of the 5q- syndrome, including (1) more severe anemia with faster kinetics than Rps14 haploinsufficiency alone and (2) pathognomonic megakaryocyte morphology. Read More

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http://www.nature.com/articles/s41375-018-0350-3
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http://dx.doi.org/10.1038/s41375-018-0350-3DOI Listing
January 2019
8 Reads

Immune cell constitution in bone marrow microenvironment predicts outcome in adult ALL.

Leukemia 2019 Jan 11. Epub 2019 Jan 11.

Hematology Research Unit Helsinki, University of Helsinki, Helsinki, Finland.

As novel immunological treatments are gaining a foothold in the treatment of acute lymphoblastic leukemia (ALL), it is elemental to examine ALL immunobiology in more detail. We used multiplexed immunohistochemistry (mIHC) to study the immune contexture in adult precursor B cell ALL bone marrow (BM). In addition, we developed a multivariate risk prediction model that stratified a poor survival group based on clinical parameters and mIHC data. Read More

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http://dx.doi.org/10.1038/s41375-018-0360-1DOI Listing
January 2019
2 Reads

Genetic and transcriptional landscape of plasma cells in POEMS syndrome.

Leukemia 2019 Jan 11. Epub 2019 Jan 11.

Department of Hematology, Chiba University Hospital, Chiba, Japan.

POEMS syndrome is a rare paraneoplastic disease associated with monoclonal plasma cells; however, the pathogenic importance of plasma cells remains unclear. We performed comprehensive genetic analyses of plasma cells in 20 patients with POEMS syndrome. Whole exome sequencing was performed in 11 cases and found a total of 308 somatic mutations in 285 genes. Read More

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http://www.nature.com/articles/s41375-018-0348-x
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http://dx.doi.org/10.1038/s41375-018-0348-xDOI Listing
January 2019
2 Reads

KIT D816 mutated/CBF-negative acute myeloid leukemia: a poor-risk subtype associated with systemic mastocytosis.

Leukemia 2019 Jan 11. Epub 2019 Jan 11.

Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany.

KIT D816 mutations (KIT D816) are strongly associated with systemic mastocytosis (SM) but are also detectable in acute myeloid leukemia (AML), where they represent an adverse prognostic factor in combination with core binding factor (CBF) fusion genes. Here, we evaluated the clinical and molecular features of KIT D816/CBF-negative (CBF) AML, a previously uncharacterized combination. All KIT D816/CBF cases (n = 40) had histologically proven SM with associated AML (SM-AML). Read More

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http://www.nature.com/articles/s41375-018-0346-z
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http://dx.doi.org/10.1038/s41375-018-0346-zDOI Listing
January 2019
8 Reads

The S505A thrombopoietin receptor mutation in childhood hereditary thrombocytosis and essential thrombocythemia is S505N: single letter amino acid code matters.

Leukemia 2019 Feb 11;33(2):563-564. Epub 2019 Jan 11.

Université catholique de Louvain, de Duve Institute and WELBIO, Brussels, Belgium.

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http://dx.doi.org/10.1038/s41375-018-0356-xDOI Listing
February 2019
1 Read

The transcriptional regulator FUBP1 influences disease outcome in murine and human myeloid leukemia.

Leukemia 2019 Jan 11. Epub 2019 Jan 11.

Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany.

The transcriptional regulator far upstream element binding protein 1 (FUBP1) acts as an oncoprotein in solid tumor entities and plays a role in the maintenance of hematopoietic stem cells. However, its potential function in leukemia is unknown. In murine models of chronic (CML) and acute myeloid leukemia (AML) induced by BCR-ABL1 and MLL-AF9, respectively, knockdown of Fubp1 resulted in prolonged survival, decreased numbers of CML progenitor cells, decreased cell cycle activity and increased apoptosis. Read More

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http://www.nature.com/articles/s41375-018-0358-8
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http://dx.doi.org/10.1038/s41375-018-0358-8DOI Listing
January 2019
10 Reads

JMJD1C-mediated metabolic dysregulation contributes to HOXA9-dependent leukemogenesis.

Leukemia 2019 Jan 8. Epub 2019 Jan 8.

Cancer and Stem Cell Biology Group, Children's Cancer Institute, University of New South Wales, Sydney, NSW 2052, Australia.

Abnormal metabolism is a fundamental hallmark of cancer and represents a therapeutic opportunity, yet its regulation by oncogenes remains poorly understood. Here, we uncover that JMJD1C, a jumonji C (JmjC)-containing H3K9 demethylase, is a critical regulator of aberrant metabolic processes in homeobox A9 (HOXA9)-dependent acute myeloid leukemia (AML). JMJD1C overexpression increases in vivo cell proliferation and tumorigenicity through demethylase-independent upregulation of a glycolytic and oxidative program, which sustains leukemic cell bioenergetics and contributes to an aggressive AML phenotype in vivo. Read More

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http://www.nature.com/articles/s41375-018-0354-z
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http://dx.doi.org/10.1038/s41375-018-0354-zDOI Listing
January 2019
11 Reads
10.431 Impact Factor

The genetics and clinical characteristics of children morphologically diagnosed as acute promyelocytic leukemia.

Leukemia 2018 Dec 21. Epub 2018 Dec 21.

Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Acute promyelocytic leukemia (APL) is characterized by t(15;17)(q22;q21), resulting in a PML-RARA fusion that is the master driver of APL. A few cases that cannot be identified with PML-RARA by using conventional methods (karyotype analysis, FISH, and RT-PCR) involve abnormal promyelocytes that are fully in accordance with APL in morphology, cytochemistry, and immunophenotype. To explore the mechanisms involved in pathogenesis and recurrence of morphologically diagnosed APL, we performed comprehensive variant analysis by next-generation sequencing in 111 pediatric patients morphologically diagnosed as APL. Read More

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http://dx.doi.org/10.1038/s41375-018-0338-zDOI Listing
December 2018
3 Reads

Targeting nuclear β-catenin as therapy for post-myeloproliferative neoplasm secondary AML.

Leukemia 2018 Dec 21. Epub 2018 Dec 21.

The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA.

Transformation of post-myeloproliferative neoplasms into secondary (s) AML exhibit poor clinical outcome. In addition to increased JAK-STAT and PI3K-AKT signaling, post-MPN sAML blast progenitor cells (BPCs) demonstrate increased nuclear β-catenin levels and TCF7L2 (TCF4) transcriptional activity. Knockdown of β-catenin or treatment with BC2059 that disrupts binding of β-catenin to TBL1X (TBL1) depleted nuclear β-catenin levels. Read More

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http://www.nature.com/articles/s41375-018-0334-3
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http://dx.doi.org/10.1038/s41375-018-0334-3DOI Listing
December 2018
11 Reads
10.431 Impact Factor

Bone marrow MSCs in MDS: contribution towards dysfunctional hematopoiesis and potential targets for disease response to hypomethylating therapy.

Leukemia 2018 Dec 21. Epub 2018 Dec 21.

Department of Hematology, Singapore General Hospital, Singapore, Singapore.

The study of myelodysplastic syndromes (MDS) in murine models has now indicated the possible involvement of the bone marrow microenvironment in the generation of dysplastic hematopoietic cells. However, there is scant work on patient samples and the role of hypomethylating agents on the bone marrow stromal cells of MDS patients is unclear. We show that human MDS-MSCs exhibit phenotypic, transcriptomic and epigenetic abnormalities. Read More

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http://dx.doi.org/10.1038/s41375-018-0310-yDOI Listing
December 2018
2 Reads

High cortactin expression in B-cell acute lymphoblastic leukemia is associated with increased transendothelial migration and bone marrow relapse.

Leukemia 2018 Dec 20. Epub 2018 Dec 20.

Unidad de Investigación Médica en Enfermedades Oncológicas, UMAE Hospital Oncología, Instituto Mexicano del Seguro Social, Mexico City, Mexico.

Cancer is a major cause of death in children worldwide, with B-lineage cell acute lymphoblastic leukemia (B-ALL) being the most frequent childhood malignancy. Relapse, treatment failure and organ infiltration worsen the prognosis, warranting a better understanding of the implicated mechanisms. Cortactin is an actin-binding protein involved in cell adhesion and migration that is overexpressed in many solid tumors and in adult B-cell chronic lymphocytic leukemia. Read More

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http://dx.doi.org/10.1038/s41375-018-0333-4DOI Listing
December 2018
4 Reads

PRR14L mutations are associated with chromosome 22 acquired uniparental disomy, age-related clonal hematopoiesis and myeloid neoplasia.

Leukemia 2018 Dec 20. Epub 2018 Dec 20.

Faculty of Medicine, University of Southampton, Southampton, UK.

Acquired uniparental disomy (aUPD, also known as copy-neutral loss of heterozygosity) is a common feature of cancer cells and characterized by extended tracts of somatically-acquired homozygosity without any concurrent loss or gain of genetic material. The presumed genetic targets of many regions of aUPD remain unknown. Here we describe the association of chromosome 22 aUPD with mutations that delete the C-terminus of PRR14L in patients with chronic myelomonocytic leukemia (CMML), related myeloid neoplasms and age-related clonal hematopoiesis (ARCH). Read More

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http://dx.doi.org/10.1038/s41375-018-0340-5DOI Listing
December 2018
2 Reads

Recurrent activating STAT5B N642H mutation in myeloid neoplasms with eosinophilia.

Leukemia 2019 Feb 20;33(2):415-425. Epub 2018 Dec 20.

Faculty of Medicine, University of Southampton, Southampton, UK.

Determining the underlying cause of persistent eosinophilia is important for effective clinical management but remains a diagnostic challenge in many cases. We identified STAT5B N642H, an established oncogenic mutation, in 27/1715 (1.6%) cases referred for investigation of eosinophilia. Read More

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http://www.nature.com/articles/s41375-018-0342-3
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http://dx.doi.org/10.1038/s41375-018-0342-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365490PMC
February 2019
6 Reads

Late treatment-related mortality versus competing causes of death after allogeneic transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia.

Leukemia 2018 Dec 20. Epub 2018 Dec 20.

University Hospital Eppendorf, Hamburg, Germany.

The causes and rates of late patient-mortality following alloHCT for myelodysplastic syndromes or secondary acute myeloid leukemia were studied, to assess the contribution of relapse-related, treatment-related, and population factors. Data from EBMT on 6434 adults, who received a first alloHCT from January 2000 to December 2012, were retrospectively studied using combined land-marking, relative-survival methods and multi-state modeling techniques. Median age at alloHCT increased from 49 to 58 years, and the number of patients aged ≥65 years at alloHCT increased from 5 to 17%. Read More

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http://www.nature.com/articles/s41375-018-0302-y
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http://dx.doi.org/10.1038/s41375-018-0302-yDOI Listing
December 2018
13 Reads

CLL2-BIG: sequential treatment with bendamustine, ibrutinib and obinutuzumab (GA101) in chronic lymphocytic leukemia.

Leukemia 2018 Dec 19. Epub 2018 Dec 19.

Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, CECAD Cluster of Excellence at the University of Cologne, Clinical Research Unit (KFO) 286, German CLL Study Group, University of Cologne, Cologne, Germany.

Obinutuzumab (GA101) and ibrutinib show excellent efficacy for treatment of chronic lymphocytic leukemia (CLL). Preclinical investigations and a complementary safety profile were in support of testing their combined use. The exploratory CLL2-BIG-trial evaluated a sequential combination therapy following a recently proposed strategy. Read More

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http://dx.doi.org/10.1038/s41375-018-0313-8DOI Listing
December 2018
3 Reads

Improved survival for children and young adolescents with acute myeloid leukemia: a Dutch study on incidence, survival and mortality.

Leukemia 2018 Dec 19. Epub 2018 Dec 19.

Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands.

Variation in survival of pediatric acute myeloid leukemia (pAML) over time and between Western European countries exists. The aim of the current study is to assess the progress made for the Dutch pAML population (0-17 years) during 1990-2015, based on trends in incidence, survival and mortality. Data from the population-based Netherlands Cancer Registry were merged with leukemia-related characteristics and treatment specifics from the Dutch Childhood Leukemia Study Group (Dutch Childhood Oncology Group (DCOG) from 2002 onwards). Read More

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http://www.nature.com/articles/s41375-018-0314-7
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http://dx.doi.org/10.1038/s41375-018-0314-7DOI Listing
December 2018
13 Reads

Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome.

Leukemia 2019 Feb 16;33(2):379-389. Epub 2018 Dec 16.

Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.

Glasdegib is a Hedgehog pathway inhibitor. This phase II, randomized, open-label, multicenter study (ClinicalTrials.gov, NCT01546038) evaluated the efficacy of glasdegib plus low-dose cytarabine (LDAC) in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome unsuitable for intensive chemotherapy. Read More

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http://dx.doi.org/10.1038/s41375-018-0312-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365492PMC
February 2019
2 Reads

The importance of B cell receptor isotypes and stereotypes in chronic lymphocytic leukemia.

Leukemia 2019 Feb 16;33(2):287-298. Epub 2018 Dec 16.

Department of Leukemia, Unit 428, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

B cell receptor (BCR) signaling is a central pathway promoting the survival and proliferation of normal and malignant B cells. Chronic lymphocytic leukemia (CLL) arises from mature B cells, expressing functional BCRs, mainly of immunoglobulin M (IgM) and IgD isotypes. Importantly, 30% of CLL patients express quasi-identical BCRs, the so-called "stereotyped" receptors, indicating the existence of common antigenic determinants, which may drive disease initiation and favor its progression. Read More

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http://dx.doi.org/10.1038/s41375-018-0303-xDOI Listing
February 2019
2 Reads

Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia.

Leukemia 2018 Dec 14. Epub 2018 Dec 14.

Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. Read More

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http://dx.doi.org/10.1038/s41375-018-0307-6DOI Listing
December 2018
2 Reads

Refining AML outcome prediction.

Leukemia 2019 Feb 14;33(2):283-284. Epub 2018 Dec 14.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

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http://dx.doi.org/10.1038/s41375-018-0317-4DOI Listing
February 2019
2 Reads

Optimized induction of mitochondrial apoptosis for chemotherapy-free treatment of BCR-ABL+acute lymphoblastic leukemia.

Leukemia 2018 Dec 13. Epub 2018 Dec 13.

Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.

BCR-ABL+acute lymphoblastic leukemia (ALL) in adults has a poor prognosis with allogeneic stem cell transplantation (SCT) considered the best curative option for suitable patients. We here characterize the curative potential of BH3-mimetics differentially targeting mitochondrial BCL2-family members using a combination therapy approach with dexamethasone and tyrosine kinase inhibitors targeting BCR-ABL. In BCR-ABL + ALL BH3-mimetics act by redistribution of mitochondrial activator BIM, which is strongly required for cytotoxicity of the BCL2-specific BH3-mimetic ABT-199, tyrosine kinase inhibitors (TKIs) and dexamethasone. Read More

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http://dx.doi.org/10.1038/s41375-018-0315-6DOI Listing
December 2018
2 Reads

Epidemiology of bloodstream infections in patients with chronic lymphocytic leukemia: a longitudinal nation-wide cohort study.

Leukemia 2018 Dec 13. Epub 2018 Dec 13.

Department of Haematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Patients with chronic lymphocytic leukemia (CLL) have a high risk of bloodstream infections (BSI). BSI cause significant morbidity and mortality among CLL patients; approximately one-third of fatalities in CLL list infections as cause of death. All CLL patients in Denmark diagnosed between 2008 and 2016 were followed through registries for the event of a BSI. Read More

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http://dx.doi.org/10.1038/s41375-018-0316-5DOI Listing
December 2018
2 Reads

Genomic and transcriptomic landscapes of Epstein-Barr virus in extranodal natural killer T-cell lymphoma.

Leukemia 2018 Dec 13. Epub 2018 Dec 13.

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

Extranodal natural killer T-cell lymphoma (nasal type; NKTCL) is an aggressive malignancy strongly associated with Epstein-Barr virus (EBV) infection. However, the role of EBV in NKTCL development is unclear, largely due to the lack of information about EBV genome and transcriptome in NKTCL. Here, using high-throughput sequencing, we obtained whole genome (n = 27) and transcriptome datasets (n = 18) of EBV derived from NKTCL tumor biopsies. Read More

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http://dx.doi.org/10.1038/s41375-018-0324-5DOI Listing
December 2018
3 Reads
10.431 Impact Factor

Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis.

Leukemia 2018 Dec 12. Epub 2018 Dec 12.

Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, CIBERONC Pamplona, Pamplona, Spain.

Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N = 30). Read More

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http://dx.doi.org/10.1038/s41375-018-0308-5DOI Listing
December 2018
3 Reads

CD34CD38 leukemic stem cell frequency to predict outcome in acute myeloid leukemia.

Leukemia 2018 Dec 12. Epub 2018 Dec 12.

Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.

Current risk algorithms are primarily based on pre-treatment factors and imperfectly predict outcome in acute myeloid leukemia (AML). We introduce and validate a post-treatment approach of leukemic stem cell (LSC) assessment for prediction of outcome. LSC containing CD34+CD38- fractions were measured using flow cytometry in an add-on study of the HOVON102/SAKK trial. Read More

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http://dx.doi.org/10.1038/s41375-018-0326-3DOI Listing
December 2018
3 Reads

JAK2V617F but not CALR mutations confer increased molecular responses to interferon-α via JAK1/STAT1 activation.

Leukemia 2018 Nov 23. Epub 2018 Nov 23.

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

Pegylated interferon-α (peg-IFNa) treatment induces molecular responses (MR) in patients with myeloproliferative neoplasms (MPNs), including partial MR (PMR) in 30-40% of patients. Here, we compared the efficacy of IFNa treatment in JAK2V617F- vs. calreticulin (CALR)-mutated cells and investigated the mechanisms of differential response. Read More

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http://dx.doi.org/10.1038/s41375-018-0295-6DOI Listing
November 2018
13 Reads