3,231 results match your criteria Clinical 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

View Article

Download full-text PDF

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

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

Leukemia 2019 Apr 9. Epub 2019 Apr 9.

ProfilExpert, Lyon, France.

View Article

Download full-text PDF

Source
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.

View Article

Download full-text PDF

Source
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

View Article

Download full-text PDF

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

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

View Article

Download full-text PDF

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

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41375-019-0446-4
Publisher Site
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

View Article

Download full-text PDF

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

View Article

Download full-text PDF

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

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

View Article

Download full-text PDF

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

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

View Article

Download full-text PDF

Source
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

View Article

Download full-text PDF

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

Nucleolin promotes Wnt signaling in human hematopoietic stem/progenitor cells.

Leukemia 2019 Apr 22;33(4):1052-1054. Epub 2019 Feb 22.

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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-019-0401-4DOI Listing

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

Leukemia 2019 Feb 20. Epub 2019 Feb 20.

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

In the original version of this article there was a mistake in the spelling of the author Sujoy Ghosh, originally spelt Sujoy Gosh. This has now been corrected in both the PDF and HTML versions of the article. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-019-0406-zDOI Listing
February 2019

Response of high-risk MDS to azacitidine and lenalidomide is impacted by baseline and acquired mutations in a cluster of three inositide-specific genes.

Leukemia 2019 Feb 20. Epub 2019 Feb 20.

Cellular Signalling Laboratory, Human Anatomy Section, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

Specific myeloid-related and inositide-specific gene mutations can be linked to myelodysplastic syndromes (MDS) pathogenesis and therapy. Here, 44 higher-risk MDS patients were treated with azacitidine and lenalidomide and mutations analyses were performed at baseline and during the therapy. Results were then correlated to clinical outcome, overall survival (OS), leukemia-free-survival (LFS) and response to therapy. Read More

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41375-019-0416-x
Publisher Site
http://dx.doi.org/10.1038/s41375-019-0416-xDOI Listing
February 2019
6 Reads
10.431 Impact Factor

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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-019-0395-yDOI Listing
February 2019
6 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

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41375-019-0379-y
Publisher Site
http://dx.doi.org/10.1038/s41375-019-0379-yDOI Listing
February 2019
10 Reads

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

Leukemia 2019 Mar 31;33(3):597-611. 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

View Article

Download full-text PDF

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

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

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41375-019-0389-9
Publisher Site
http://dx.doi.org/10.1038/s41375-019-0389-9DOI Listing
January 2019
6 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 Apr 30;33(4):844-862. 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-019-0388-xDOI Listing
April 2019
2 Reads

Rethinking clinical trial endpoints in myelodysplastic syndromes.

Leukemia 2019 Mar 30;33(3):570-575. 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-018-0367-7DOI Listing
March 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

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41375-018-0361-0
Publisher Site
http://dx.doi.org/10.1038/s41375-018-0361-0DOI Listing
January 2019
12 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

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41375-019-0381-4
Publisher Site
http://dx.doi.org/10.1038/s41375-019-0381-4DOI Listing
January 2019
8 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

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41375-019-0378-z
Publisher Site
http://dx.doi.org/10.1038/s41375-019-0378-zDOI Listing
January 2019
1 Read

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

Leukemia 2019 Mar 28;33(3):588-596. 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

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41375-019-0383-2
Publisher Site
http://dx.doi.org/10.1038/s41375-019-0383-2DOI Listing
March 2019
9 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

View Article

Download full-text PDF

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

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

Leukemia 2019 Apr 25;33(4):863-883. 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-018-0362-zDOI Listing
April 2019
2 Reads

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.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-018-0374-8DOI Listing
January 2019
2 Reads

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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-018-0375-7DOI Listing
January 2019
5 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

View Article

Download full-text PDF

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

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

Leukemia 2019 Mar 22;33(3):567-569. Epub 2019 Jan 22.

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

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41375-018-0363-y
Publisher Site
http://dx.doi.org/10.1038/s41375-018-0363-yDOI Listing
March 2019
8 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.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-018-0296-5DOI Listing
January 2019
3 Reads

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

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41375-018-0357-9
Publisher Site
http://dx.doi.org/10.1038/s41375-018-0357-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365380PMC
February 2019
37 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

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41375-018-0350-3
Publisher Site
http://dx.doi.org/10.1038/s41375-018-0350-3DOI Listing
January 2019
15 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-018-0360-1DOI Listing
January 2019
3 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

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41375-018-0348-x
Publisher Site
http://dx.doi.org/10.1038/s41375-018-0348-xDOI Listing
January 2019
4 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

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41375-018-0346-z
Publisher Site
http://dx.doi.org/10.1038/s41375-018-0346-zDOI Listing
January 2019
16 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.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-018-0356-xDOI Listing
February 2019
3 Reads

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

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41375-018-0358-8
Publisher Site
http://dx.doi.org/10.1038/s41375-018-0358-8DOI Listing
January 2019
17 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

View Article

Download full-text PDF

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