11,416 results match your criteria Leukemia[Journal]


Aberrant Wnt signaling in multiple myeloma: molecular mechanisms and targeting options.

Leukemia 2019 Feb 15. Epub 2019 Feb 15.

Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Aberrant activation of Wnt/β-catenin signaling plays a central role in the pathogenesis of a wide variety of malignancies and is typically caused by mutations in core Wnt pathway components driving constitutive, ligand-independent signaling. In multiple myelomas (MMs), however, these pathway intrinsic mutations are rare despite the fact that most tumors display aberrant Wnt pathway activity. Recent studies indicate that this activation is caused by genetic and epigenetic lesions of Wnt regulatory components, sensitizing MM cells to autocrine Wnt ligands and paracrine Wnts emanating from the bone marrow niche. Read More

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http://dx.doi.org/10.1038/s41375-019-0404-1DOI Listing
February 2019

RUNX proteins desensitize multiple myeloma to lenalidomide via protecting IKZFs from degradation.

Leukemia 2019 Feb 13. Epub 2019 Feb 13.

Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Ikaros family zinc finger protein 1 and 3 (IKZF1 and IKZF3) are transcription factors that promote multiple myeloma (MM) proliferation. The immunomodulatory imide drug (IMiD) lenalidomide promotes myeloma cell death via Cereblon (CRBN)-dependent ubiquitylation and proteasome-dependent degradation of IKZF1 and IKZF3. Although IMiDs have been used as first-line drugs for MM, the overall survival of refractory MM patients remains poor and demands the identification of novel agents to potentiate the therapeutic effect of IMiDs. Read More

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http://dx.doi.org/10.1038/s41375-019-0403-2DOI Listing
February 2019
2 Reads

Genetic mechanisms of primary chemotherapy resistance in pediatric acute myeloid leukemia.

Leukemia 2019 Feb 13. Epub 2019 Feb 13.

Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Acute myeloid leukemias (AML) are characterized by mutations of tumor suppressor and oncogenes, involving distinct genes in adults and children. While certain mutations have been associated with the increased risk of AML relapse, the genomic landscape of primary chemotherapy-resistant AML is not well defined. As part of the TARGET initiative, we performed whole-genome DNA and transcriptome RNA and miRNA sequencing analysis of pediatric AML with failure of induction chemotherapy. Read More

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http://dx.doi.org/10.1038/s41375-019-0402-3DOI Listing
February 2019

EZH2 is overexpressed in transitional preplasmablasts and is involved in human plasma cell differentiation.

Leukemia 2019 Feb 12. Epub 2019 Feb 12.

IGH, CNRS, University of Montpellier, Montpellier, France.

Plasma cells (PCs) play a major role in the defense of the host organism against pathogens. We have shown that PC generation can be modeled using multi-step culture systems that reproduce the sequential cell differentiation occurring in vivo. Using this unique model, we investigated the role of EZH2 during PC differentiation (PCD) using H3K27me3 and EZH2 ChIP-binding profiles. Read More

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http://dx.doi.org/10.1038/s41375-019-0392-1DOI Listing
February 2019
10.431 Impact Factor

Destabilization of AETFC through C/EBPα-mediated repression of LYL1 contributes to t(8;21) leukemic cell differentiation.

Leukemia 2019 Feb 12. Epub 2019 Feb 12.

State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.1038/s41375-019-0398-8DOI Listing
February 2019

S100A9-induced overexpression of PD-1/PD-L1 contributes to ineffective hematopoiesis in myelodysplastic syndromes.

Leukemia 2019 Feb 8. Epub 2019 Feb 8.

Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Myelodysplastic syndromes (MDS) are characterized by dysplastic and ineffective hematopoiesis that can result from aberrant expansion and activation of myeloid-derived suppressor cells (MDSCs) within the bone marrow (BM) niche. MDSCs produce S100A9, which mediates premature death of hematopoietic stem and progenitor cells (HSPCs). The PD-1/PD-L1 immune checkpoint impairs immune responses by inducing T-cell exhaustion and apoptosis, but its role in MDS is uncharacterized. Read More

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http://dx.doi.org/10.1038/s41375-019-0397-9DOI Listing
February 2019
1 Read

Prognostic restaging at the time of second-line therapy in patients with AL amyloidosis.

Leukemia 2019 Feb 8. Epub 2019 Feb 8.

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

It is well known that staging of patients with AL amyloidosis at diagnosis predicts for survival, but there is a paucity of literature delineating the prognostic value of these systems at relapse. We evaluated the prognostic value of AL staging among 413 patients initiated with second-line therapy between 2000 and 2015. Both the Revised Mayo 2012 and the European revision of Mayo 2004 staging systems were used. Read More

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http://dx.doi.org/10.1038/s41375-019-0400-5DOI Listing
February 2019

The mechanistic study behind suppression of GVHD while retaining GVL activities by myeloid-derived suppressor cells.

Leukemia 2019 Feb 8. Epub 2019 Feb 8.

Center for Immunotherapy Research, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX, 77030, USA.

Graft-versus-host disease (GVHD) is a major barrier to the widespread use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating hematologic malignancies. Myeloid-derived suppressor cells (MDSCs) have been recognized as crucial immunosuppressive cells in various pathologic settings. Here, we investigated whether the unique functional properties of MDSCs could be harnessed to control allo-HSCT-associated GVHD. Read More

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http://dx.doi.org/10.1038/s41375-019-0394-zDOI Listing
February 2019
1 Read

Complex karyotype in de novo acute myeloid leukemia: typical and atypical subtypes differ molecularly and clinically.

Leukemia 2019 Feb 8. Epub 2019 Feb 8.

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

Complex karyotype (CK) with ≥ 3 abnormalities is detected in 10-12% of patients with acute myeloid leukemia (AML) and associated with poor prognosis. The most common unbalanced abnormalities found in CK result in loss of material from the 5q, 7q, and/or 17p chromosome arms. The presence of 5q, 7q, and/or 17p abnormalities denotes typical CK and their absence denotes atypical CK. Read More

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http://www.nature.com/articles/s41375-019-0390-3
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http://dx.doi.org/10.1038/s41375-019-0390-3DOI Listing
February 2019
3 Reads

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

Data mining for mutation-specific targets in acute myeloid leukemia.

Leukemia 2019 Feb 6. Epub 2019 Feb 6.

Department of Medicine, Division of Hematology, Cancer Institute, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Three mutation-specific targeted therapies have recently been approved by the FDA for the treatment of acute myeloid leukemia (AML): midostaurin for FLT3 mutations, enasidenib for relapsed or refractory cases with IDH2 mutations, and ivosidenib for cases with an IDH1 mutation. Together, these agents offer a mutation-directed treatment approach for up to 45% of de novo adult AML cases, a welcome deluge after a prolonged drought. At the same time, a number of computational tools have recently been developed that promise to further accelerate progress in mutation-specific therapy for AML and other cancers. Read More

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http://www.nature.com/articles/s41375-019-0387-y
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http://dx.doi.org/10.1038/s41375-019-0387-yDOI Listing
February 2019
3 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

A novel method for detecting the cellular stemness state in normal and leukemic human hematopoietic cells can predict disease outcome and drug sensitivity.

Leukemia 2019 Jan 31. Epub 2019 Jan 31.

Department of Pathology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.

Acute leukemia is an aggressive blood malignancy with low survival rates. A high expression of stem-like programs in leukemias predicts poor prognosis and is assumed to act in an aberrant fashion in the phenotypically heterogeneous leukemia stem cell (LSC) population. A lack of suitable genome engineering tools that can isolate LSCs based on their stemness precludes their comprehensive examination and full characterization. Read More

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http://www.nature.com/articles/s41375-019-0386-z
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http://dx.doi.org/10.1038/s41375-019-0386-zDOI Listing
January 2019
5 Reads

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

What is the best first-line treatment for POEMS syndrome: autologous transplantation, melphalan and dexamethasone, or lenalidomide and dexamethasone?

Leukemia 2019 Jan 30. Epub 2019 Jan 30.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

POEMS syndrome is a rare plasma cell dyscrasia. This study compared the responses to and survival of 347 POEMS syndrome patients given three first-line treatment regimens: autologous stem cell transplantation (ASCT, N = 165) and melphalan + dexamethasone (MDex, N = 79), or lenalidomide + dexamethasone (LDex, N = 103). After a median 45-month follow-up, overall hematologic complete remission (CR) was 46. Read More

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http://dx.doi.org/10.1038/s41375-019-0391-2DOI Listing
January 2019
2 Reads

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
2 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

Creating novel translation inhibitors to target pro-survival proteins in chronic lymphocytic leukemia.

Leukemia 2019 Jan 30. Epub 2019 Jan 30.

Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

The viability of chronic lymphocytic leukemia (CLL) is critically dependent upon staving off death by apoptosis, a hallmark of CLL pathophysiology. The recognition that Mcl-1, a major component of the anti-apoptotic response, is intrinsically short-lived and must be continually resynthesized suggested a novel therapeutic approach. Pateamine A (PatA), a macrolide marine natural product, inhibits cap-dependent translation by binding to the initiation factor eIF4A. Read More

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http://dx.doi.org/10.1038/s41375-018-0364-xDOI Listing
January 2019

New roles for B cell receptor associated kinases: when the B cell is not the target.

Leukemia 2019 Jan 30. Epub 2019 Jan 30.

Department I of Internal Medicine, University Hospital of Cologne; Center for Integrated Oncology Cologne-Bonn; CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases; Center for Molecular Medicine Cologne, University of Cologne, 50931, Cologne, Germany.

Targeting of B cell receptor associated kinases (BAKs), such as Bruton's tyrosine kinase (BTK) or phosphoinositol-3-kinase (PI3K) delta, by specific inhibitors has revolutionized the therapy of B lymphoid malignancies. BAKs are critical signaling transducers of BCR signaling and seem relevant in B cell lymphoma pathogenesis. The functional relevance of BTK for lymphoid malignancies is strongly supported by the observation that resistance to therapy in CLL patients treated with BTK inhibitors such as ibrutinib is often associated with mutations in genes coding for BTK or Phospholipase-C gamma (PLCɣ). Read More

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http://www.nature.com/articles/s41375-018-0366-8
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http://dx.doi.org/10.1038/s41375-018-0366-8DOI Listing
January 2019
2 Reads

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
4 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

Ixazomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma: long-term follow-up including ixazomib maintenance.

Leukemia 2019 Jan 29. Epub 2019 Jan 29.

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

Triplet combinations containing a proteasome inhibitor are a standard of care in newly diagnosed multiple myeloma (NDMM). We examined the long-term efficacy and safety of the all-oral combination of weekly ixazomib plus lenalidomide-dexamethasone (IRd), followed by single-agent ixazomib maintenance in NDMM patients. Of 65 enrolled patients, 53 received ixazomib 4 mg (days 1, 8, and 15) plus lenalidomide 25 mg (days 1-21) and dexamethasone 40 mg (days 1, 8, 15, and 22) for up to twelve 28-day induction cycles. Read More

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http://dx.doi.org/10.1038/s41375-019-0384-1DOI 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

A germline HLTF mutation in familial MDS induces DNA damage accumulation through impaired PCNA polyubiquitination.

Leukemia 2019 Jan 29. Epub 2019 Jan 29.

Department of Hematology and Oncology, The University of Tokyo, Tokyo, Japan.

Although several causal genes of familial myelodysplastic syndromes (MDS) have been identified, the genetic landscape and the molecular pathogenesis are not totally understood. To explore novel driver genes and their pathogenetic significance, we performed whole-exome sequence analysis of four individuals from a familial MDS pedigree and 10 candidate single-nucleotide variants (C9orf43, CYP7B1, EFHB, ENTPD7, FAM160B2, HELZ2, HLTF, INPP5J, ITPKB, and RYK) were identified. Knockdown screening revealed that Hltf downregulation enhanced colony-forming capacity of primary murine bone marrow (BM) stem/progenitor cells. Read More

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http://dx.doi.org/10.1038/s41375-019-0385-0DOI Listing
January 2019
1 Read

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
3 Reads

Sequentially inducible mouse models reveal that Npm1 mutation causes malignant transformation of Dnmt3a-mutant clonal hematopoiesis.

Leukemia 2019 Jan 28. Epub 2019 Jan 28.

The Jackson Laboratory, Bar Harbor, ME, USA.

Clonal hematopoiesis (CH) is a common aging-associated condition with increased risk of hematologic malignancy. Knowledge of the mechanisms driving evolution from CH to overt malignancy has been hampered by a lack of in vivo models that orthogonally activate mutant alleles. Here, we develop independently regulatable mutations in DNA methyltransferase 3A (Dnmt3a) and nucleophosmin 1 (Npm1), observed in human CH and AML, respectively. Read More

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http://www.nature.com/articles/s41375-018-0368-6
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http://dx.doi.org/10.1038/s41375-018-0368-6DOI 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

Inflammation-induced glycolytic switch controls suppressivity of mesenchymal stem cells via STAT1 glycosylation.

Leukemia 2019 Jan 24. Epub 2019 Jan 24.

Department of Medicine 5 for Hematology and Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054, Erlangen, Germany.

Mesenchymal stem cells (MSCs) represent key contributors to tissue homeostasis and promising therapeutics for hyperinflammatory conditions including graft-versus-host disease. Their immunomodulatory effects are controlled by microenvironmental signals. The MSCs' functional response towards inflammatory cues is known as MSC-"licensing" and includes indoleamine 2,3-dioxygenase (IDO) upregulation. Read More

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http://dx.doi.org/10.1038/s41375-018-0376-6DOI 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

CEBPA-mutated leukemia is sensitive to genetic and pharmacological targeting of the MLL1 complex.

Leukemia 2019 Jan 24. Epub 2019 Jan 24.

Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.

The gene encoding the transcription factor C/EBPα is mutated in 10-15% of acute myeloid leukemia (AML) patients. N-terminal CEBPA mutations cause ablation of full-length C/EBPα without affecting the expression of a shorter oncogenic isoform, termed p30. The mechanistic basis of p30-induced leukemogenesis is incompletely understood. Read More

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http://dx.doi.org/10.1038/s41375-019-0382-3DOI Listing
January 2019
1 Read

Azacitidine is effective for targeting leukemia-initiating cells in juvenile myelomonocytic leukemia.

Leukemia 2019 Jan 24. Epub 2019 Jan 24.

Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

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http://dx.doi.org/10.1038/s41375-018-0343-2DOI Listing
January 2019
1 Read

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
4 Reads

Characteristic gene alterations in primary gastrointestinal T- and NK-cell lymphomas.

Leukemia 2019 Jan 23. Epub 2019 Jan 23.

Department of Pathology, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea.

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http://dx.doi.org/10.1038/s41375-018-0309-4DOI Listing
January 2019

The prognostic potential of monitoring disease dynamics in NPM1-positive acute myeloid leukemia.

Leukemia 2019 Jan 23. Epub 2019 Jan 23.

Institute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, TU Dresden, Dresden, Germany.

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http://dx.doi.org/10.1038/s41375-018-0371-yDOI Listing
January 2019

Mutant p53 enhances leukemia-initiating cell self-renewal to promote leukemia development.

Leukemia 2019 Jan 23. Epub 2019 Jan 23.

Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

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http://dx.doi.org/10.1038/s41375-019-0377-0DOI Listing
January 2019
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The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview.

Leukemia 2019 Jan 23. Epub 2019 Jan 23.

Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Ludwig-Maximilians-Universität München, Munich, Germany.

There are different BCR-ABL1 fusion genes that are translated into proteins that are different from each other, yet all leukemogenic, causing chronic myeloid leukemia (CML) or acute lymphoblastic leukemia. Their frequency has never been systematically investigated. In a series of 45503 newly diagnosed CML patients reported from 45 countries, it was found that the proportion of e13a2 (also known as b2a2) and of e14a2 (also known as b3a2), including the cases co-expressing e14a2 and e13a2, was 37. Read More

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http://www.nature.com/articles/s41375-018-0341-4
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http://dx.doi.org/10.1038/s41375-018-0341-4DOI Listing
January 2019
4 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
2 Reads

Functional cooperativity of p97 and histone deacetylase 6 in mediating DNA repair in mantle cell lymphoma cells.

Leukemia 2019 Jan 21. Epub 2019 Jan 21.

Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Cancer Center, Kanas City, KS, USA.

p97 is an ATPase that works in concert with histone deacetylase 6 (HDAC6), to facilitate the degradation of misfolded proteins by autophagosomes. p97 has also been implicated in DNA repair and maintaining genomic stability. In this study, we determined the effect of combined inhibition of p97 and HDAC6 activities in mantle cell lymphoma (MCL) cells. Read More

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http://dx.doi.org/10.1038/s41375-018-0355-yDOI Listing
January 2019
2 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
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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