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    3043 results match your criteria Clinical Leukemia [Journal]

    1 OF 61

    A decade of progress in myelodysplastic syndrome with chromosome 5q deletion.
    Leukemia 2018 Jan 30. Epub 2018 Jan 30.
    Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris Université Paris 7, Paris, France.
    There are few instances in oncology where reciprocal clinical and laboratory translation studies have accelerated the understanding of disease biology and treatment more so than the decade following the Food and Drug Administration (FDA) approval of lenalidomide (Revlimid; Celgene Corporation, Summit, NJ, USA) for the treatment of patients with myelodysplastic syndrome (MDS) and chromosome 5q deletion (del(5q)). Lenalidomide was approved by the FDA in December 2005 on the merits of a multicenter phase 2 study, which demonstrated sustained and prolonged transfusion independence in the majority of participants. Since then, del(5q) MDS has emerged as one of the best characterized bone marrow malignancies and, in particular, has raised our understanding as to how allelic haplodeficiency underlies both its hematological phenotype and the selective sensitivity to lenalidomide by virtue of synthetic lethality. Read More

    Oncogenic activation of JAK3-STAT signaling confers clinical sensitivity to PRN371, a novel selective and potent JAK3 inhibitor, in natural killer/T-cell lymphoma.
    Leukemia 2018 Feb 2. Epub 2018 Feb 2.
    Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore.
    Aberrant activation of the JAK3-STAT signaling pathway is a characteristic feature of many hematological malignancies. In particular, hyperactivity of this cascade has been observed in natural killer/T-cell lymphoma (NKTL) cases. Although the first-in-class JAK3 inhibitor tofacitinib blocks JAK3 activity in NKTL both in vitro and in vivo, its clinical utilization in cancer therapy has been limited by the pan-JAK inhibition activity. Read More

    Management of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond.
    Leukemia 2018 Feb 16;32(2):252-262. Epub 2017 Nov 16.
    Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
    Despite enormous advances, management of multiple myeloma (MM) remains challenging. Multiple factors impact the decision to treat or which regimen to use at MM relapse/progression. Recent major randomized controlled trials (RCTs) showed widely varying progression-free survivals (PFS), ranging from a median of 4 months (MM-003) to 23. Read More

    Prevention and management of adverse events of Novel agents in multiple myeloma: A consensus of the european myeloma network.
    Leukemia 2017 Dec 18. Epub 2017 Dec 18.
    Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands.
    During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drugs classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events. Read More

    AZA-MS: a novel multiparameter mass spectrometry method to determine the intracellular dynamics of azacitidine therapy in vivo.
    Leukemia 2017 Nov 29. Epub 2017 Nov 29.
    Adult Cancer Program, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia.
    The cytidine analogue, 5-azacytidine (AZA; 5-AZA-cR), is the primary treatment for myelodysplastic syndrome and chronic myelomonocytic leukaemia. However, only ~50% of treated patients will respond to AZA and the drivers of AZA resistance in vivo are poorly understood. To better understand the intracellular dynamics of AZA upon therapy and decipher the molecular basis for AZA resistance, we have developed a novel, multiparameter, quantitative mass spectrometry method (AZA-MS). Read More

    Persistence of pre-leukemic clones during first remission and risk of relapse in acute myeloid leukemia.
    Leukemia 2017 Dec 18. Epub 2017 Dec 18.
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, LMU Munich, Munich, Germany.
    Some patients with acute myeloid leukemia (AML) who are in complete remission after induction chemotherapy harbor persisting pre-leukemic clones, carrying a subset of leukemia-associated somatic mutations. There is conflicting evidence on the prognostic relevance of these clones for AML relapse. Here, we characterized paired pre-treatment and remission samples from 126 AML patients for mutations in 68 leukemia-associated genes. Read More

    Drug-induced inhibition of phosphorylation of STAT5 overrides drug resistance in neoplastic mast cells.
    Leukemia 2017 Nov 29. Epub 2017 Nov 29.
    Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
    Systemic mastocytosis (SM) is a mast cell (MC) neoplasm with complex pathology and a variable clinical course. In aggressive SM (ASM) and MC leukemia (MCL), responses to conventional drugs are poor and the prognosis is dismal. R763 is a multi-kinase inhibitor that blocks the activity of Aurora-kinase-A/B, ABL1, AKT and FLT3. Read More

    Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups.
    Leukemia 2017 Dec 6. Epub 2017 Dec 6.
    Dana-Farber Cancer Institute, Harvard Medical School, LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Boston, MA, USA.
    In multiple myeloma, next generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here, we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Translocations and copy number changes (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case. Read More

    Protein arginine methyltransferase 5 has prognostic relevance and is a druggable target in multiple myeloma.
    Leukemia 2017 Nov 21. Epub 2017 Nov 21.
    Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA.
    Arginine methyltransferases critically regulate cellular homeostasis by modulating the functional outcome of their substrates. The protein arginine methyltransferase 5 (PRMT5) is an enzyme involved in growth and survival pathways promoting tumorigenesis. However, little is known about the biologic function of PRMT5 and its therapeutic potential in multiple myeloma (MM). Read More

    MiR-29b antagonizes the pro-inflammatory tumor-promoting activity of multiple myeloma-educated dendritic cells.
    Leukemia 2017 Nov 21. Epub 2017 Nov 21.
    Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy.
    Dendritic cells (DCs) have a key role in regulating tumor immunity, tumor cell growth and drug resistance. We hypothesized that multiple myeloma (MM) cells might recruit and reprogram DCs to a tumor-permissive phenotype by changes within their microRNA (miRNA) network. By analyzing six different miRNA-profiling data sets, miR-29b was identified as the only miRNA upregulated in normal mature DCs and significantly downregulated in tumor-associated DCs. Read More

    Prognostic value of antigen expression in multiple myeloma: a PETHEMA/GEM study on 1265 patients enrolled in four consecutive clinical trials.
    Leukemia 2017 Nov 3. Epub 2017 Nov 3.
    Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicadas (CIMA); Instituto de Investigación Sanitaria de Navarra (IDISNA), CIBERONC, Pamplona, Spain.
    Persistence of minimal residual disease (MRD) after treatment for myeloma predicts inferior outcomes, but within MRD-positive patients there is great heterogeneity with both early and very late relapses. Among different MRD techniques, flow cytometry provides additional information about antigen expression on tumor cells, which could potentially contribute to stratify MRD-positive patients. We investigated the prognostic value of those antigens required to monitor MRD in 1265 newly diagnosed patients enrolled in the GEM2000, GEM2005MENOS65, GEM2005MAS65 and GEM2010MAS65 protocols. Read More

    Pharmacodynamics and proteomic analysis of acalabrutinib therapy: similarity of on-target effects to ibrutinib and rationale for combination therapy.
    Leukemia 2017 Nov 3. Epub 2017 Nov 3.
    Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
    Acalabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, is associated with high overall response rates and durable remission in previously treated chronic lymphocytic leukemia (CLL); however, complete remissions were limited. To elucidate on-target and pharmacodynamic effects of acalabrutinib, we evaluated several laboratory endpoints, including proteomic changes, chemokine modulation and impact on cell migration. Pharmacological profiling of samples from acalabrutinib-treated CLL patients was used to identify strategies for achieving deeper responses, and to identify additive/synergistic combination regimens. Read More

    JAM-A as a prognostic factor and new therapeutic target in multiple myeloma.
    Leukemia 2017 Sep 28. Epub 2017 Sep 28.
    Department of Internal Medicine II, Interdisciplinary Center for Clinical Research Laboratory, University Hospital of Würzburg, Würzburg, Germany.
    Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized as a major mechanism of MM cell survival and the development of drug resistance. Here we addressed the hypothesis that the protein junctional adhesion molecule-A (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and biopsies at different disease stages. Read More

    A vicious loop of fatty acid-binding protein 4 and DNA methyltransferase 1 promotes acute myeloid leukemia and acts as a therapeutic target.
    Leukemia 2017 Oct 10. Epub 2017 Oct 10.
    The Hormel Institute, University of Minnesota, Austin, MN, USA.
    Aberrant DNA methylation mediated by deregulation of DNA methyltransferases (DNMT) is a key hallmark of acute myeloid leukemia (AML), yet efforts to target DNMT deregulation for drug development have lagged. We previously demonstrated that upregulation of fatty acid-binding protein 4 (FABP4) promotes AML aggressiveness through enhanced DNMT1-dependent DNA methylation. Here, we demonstrate that FABP4 upregulation in AML cells occurs through vascular endothelial growth factor (VEGF) signaling, thus elucidating a crucial FABP4-DNMT1 regulatory feedback loop in AML biology. Read More

    A compound chimeric antigen receptor strategy for targeting multiple myeloma.
    Leukemia 2018 Feb 27;32(2):402-412. Epub 2017 Sep 27.
    iCell Gene Therapeutics LLC, Research & Development Division, Long Island High Technology Incubator, Stony Brook, NY, USA.
    Current clinical outcomes using chimeric-antigen receptors (CARs) against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen-positive or -negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Read More

    Therapeutic targeting of CK2 in acute and chronic leukemias.
    Leukemia 2018 Jan 27;32(1):1-10. Epub 2017 Sep 27.
    Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
    CK2 is a ubiquitously expressed, constitutively active Ser/Thr protein kinase, which is considered the most pleiotropic protein kinase in the human kinome. Such a pleiotropy explains the involvement of CK2 in many cellular events. However, its predominant roles are stimulation of cell growth and prevention of apoptosis. Read More

    NG2 antigen is involved in leukemia invasiveness and central nervous system infiltration in MLL-rearranged infant B-ALL.
    Leukemia 2017 Sep 25. Epub 2017 Sep 25.
    Josep Carreras Leukemia Research Institute, Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Spain.
    Mixed-lineage leukemia (MLL)-rearranged (MLLr) infant B-cell acute lymphoblastic leukemia (iMLLr-B-ALL) has a dismal prognosis and is associated with a pro-B/mixed phenotype, therapy refractoriness and frequent central nervous system (CNS) disease/relapse. Neuron-glial antigen 2 (NG2) is specifically expressed in MLLr leukemias and is used in leukemia immunophenotyping because of its predictive value for MLLr acute leukemias. NG2 is involved in melanoma metastasis and brain development; however, its role in MLL-mediated leukemogenesis remains elusive. Read More

    NOTCH1 mutations are associated with high CD49d expression in chronic lymphocytic leukemia: link between the NOTCH1 and the NF-κB pathways.
    Leukemia 2017 Sep 22. Epub 2017 Sep 22.
    Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy.
    In chronic lymphocytic leukemia (CLL), stabilizing mutations of NOTCH1, affecting up to 10-15% of cases, have been associated to poor prognosis, disease progression and refractoriness to chemotherapy. NOTCH1 mutations are significantly overrepresented in trisomy 12 CLL, a disease subset frequently expressing CD49d, the α4 chain of the very-late-activation-4 integrin, a well-known key regulator of microenviromental interactions, and negative prognosticator in CLL. In the present study, by analysing a wide cohort of 1180 CLL, we observed a very strong association between the presence of NOTCH1 mutations and the expression of CD49d (P<0. Read More

    Clinical impact of the subclonal architecture and mutational complexity in chronic lymphocytic leukemia.
    Leukemia 2017 Sep 19. Epub 2017 Sep 19.
    Lymphoid Neoplasms Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
    Genome studies of chronic lymphocytic leukemia (CLL) have revealed the remarkable subclonal heterogeneity of the tumors, but the clinical implications of this phenomenon are not well known. We assessed the mutational status of 28 CLL driver genes by deep-targeted next-generation sequencing and copy number alterations (CNA) in 406 previously untreated patients and 48 sequential samples. We detected small subclonal mutations (0. Read More

    Clinical presentation and outcomes in light chain amyloidosis patients with non-evaluable serum free light chains.
    Leukemia 2017 Sep 18. Epub 2017 Sep 18.
    Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
    Hematologic response criteria in light chain (AL) amyloidosis require the difference in involved and uninvolved free light chains (dFLC) to be at least 5 mg/dl. We describe the clinical presentation and outcomes of newly diagnosed amyloidosis patients with dFLC <5 mg/dl (non-evaluable dFLC; 14%, n=165) compared with patients with dFLC ⩾5 mg/dl (evaluable dFLC; 86%, n=975). Patients with non-evaluable dFLC had less cardiac involvement (40% vs 80%, P<0. Read More

    High-dose methotrexate therapy significantly improved survival of adult acute lymphoblastic leukemia: a phase III study by JALSG.
    Leukemia 2017 Sep 15. Epub 2017 Sep 15.
    National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
    High-dose methotrexate (Hd-MTX) therapy has recently been applied to the treatment of adult acute lymphoblastic leukemia (ALL) based on pediatric protocols; however, its effectiveness for adult ALL has not yet been confirmed in a rigorous manner. We herein conducted a randomized phase III trial comparing Hd-MTX therapy with intermediate-dose (Id)-MTX therapy. This study was registered at UMIN-CTR (ID: C000000063). Read More

    Tyrosine kinase inhibition increases the cell surface localization of FLT3-ITD and enhances FLT3-directed immunotherapy of acute myeloid leukemia.
    Leukemia 2018 Feb 14;32(2):313-322. Epub 2017 Aug 14.
    Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
    The fms-related tyrosine kinase 3 (FLT3) receptor has been extensively studied over the past two decades with regard to oncogenic alterations that do not only serve as prognostic markers but also as therapeutic targets in acute myeloid leukemia (AML). Internal tandem duplications (ITDs) became of special interest in this setting as they are associated with unfavorable prognosis. Because of sequence-dependent protein conformational changes FLT3-ITD tends to autophosphorylate and displays a constitutive intracellular localization. Read More

    S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells.
    Leukemia 2018 Jan 7;32(1):214-223. Epub 2017 Sep 7.
    Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
    The Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma (HL) are characterised by the aberrant activation of multiple signalling pathways. Here we show that a subset of HL displays altered expression of sphingosine-1-phosphate (S1P) receptors (S1PR)s. S1P activates phosphatidylinositide 3-kinase (PI3-K) in these cells that is mediated by the increased expression of S1PR1 and the decreased expression of S1PR2. Read More

    C-terminal BRE overexpression in 11q23-rearranged and t(8;16) acute myeloid leukemia is caused by intragenic transcription initiation.
    Leukemia 2017 Sep 5. Epub 2017 Sep 5.
    Department of Molecular Biology, Faculty of Science, RIMLS, Radboud University, Nijmegen, The Netherlands.
    Overexpression of the BRE (brain and reproductive organ-expressed) gene defines a distinct pediatric and adult acute myeloid leukemia (AML) subgroup. Here we identify a promoter enriched for active chromatin marks in BRE intron 4 causing strong biallelic expression of a previously unknown C-terminal BRE transcript. This transcript starts with BRE intron 4 sequences spliced to exon 5 and downstream sequences, and if translated might code for an N terminally truncated BRE protein. Read More

    Pomalidomide-dexamethasone in refractory multiple myeloma: long-term follow-up of a multi-cohort phase II clinical trial.
    Leukemia 2017 Sep 1. Epub 2017 Sep 1.
    Division of Hematology and Medical Oncology, Department of Medicine, Mayo Clinic, Phoenix, AZ, USA.
    Despite therapeutic advances, multiple myeloma remains incurable, with limited options for patients with refractory disease. We conducted a large, multi-cohort clinical trial testing various doses and treatment schedules of pomalidomide and dexamethasone (Pom/dex) in patients with refractory multiple myeloma. Overall, 345 patients were enrolled to six cohorts based on number and type of prior lines of therapy, pomalidomide dose and schedule. Read More

    Outcomes of maintenance therapy with lenalidomide or bortezomib in multiple myeloma in the setting of early autologous stem cell transplantation.
    Leukemia 2017 Aug 14. Epub 2017 Aug 14.
    Division of Hematology, Mayo Clinic, Rochester, MN, USA.
    Post-transplant maintenance is widely used in multiple myeloma (MM); however, there is a lack of data on real-world outcomes. We have analyzed 577 patients with newly diagnosed MM undergoing early auto-transplantation between 2010 and 2015. A total of 341, 132 and 104 patients received no, lenalidomide (Len) or bortezomib (Bort) maintenance, respectively. Read More

    Toll-like receptor 2 costimulation potentiates the antitumor efficacy of CAR T Cells.
    Leukemia 2017 Aug 3. Epub 2017 Aug 3.
    Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
    Chimeric antigen receptor (CAR) T-cell immunotherapies have shown unprecedented success in treating leukemia but limited clinical efficacy in solid tumors. Here, we generated 1928zT2 and m28zT2, targeting CD19 and mesothelin, respectively, by introducing the Toll/interleukin-1 receptor domain of Toll-like receptor 2 (TLR2) to 1928z and m28z. T cells expressing 1928zT2 or m28zT2 showed improved expansion, persistency and effector function against CD19leukemia or mesothelinsolid tumors respectively in vitro and in vivo. Read More

    Activation of RHOA-VAV1 signaling in angioimmunoblastic T-cell lymphoma.
    Leukemia 2017 Aug 23. Epub 2017 Aug 23.
    Department of Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
    Somatic G17V RHOA mutations were found in 50-70% of angioimmunoblastic T-cell lymphoma (AITL). The mutant RHOA lacks GTP binding capacity, suggesting defects in the classical RHOA signaling. Here, we discovered the novel function of the G17V RHOA: VAV1 was identified as a G17V RHOA-specific binding partner via high-throughput screening. Read More

    RNA interference efficiently targets human leukemia driven by a fusion oncogene in vivo.
    Leukemia 2018 Jan 22;32(1):224-226. Epub 2017 Aug 22.
    Department of Hematology, Hemostasis, Oncology and Stem cell Transplantation, Hannover Medical School, Hannover, Germany.

    Differences between BCL2-break positive and negative follicular lymphoma unraveled by whole-exome sequencing.
    Leukemia 2017 Aug 21. Epub 2017 Aug 21.
    Institute of Pathology, University of Würzburg, Würzburg, Würzburg, Germany.
    Depending on disease stage follicular lymphoma (FL) lack the t(14;18) in ~15-~50% of cases. Nevertheless, most of these cases express BCL2. To elucidate mechanisms triggering BCL2 expression and promoting pathogenesis in t(14;18)-negative FL, exonic single-nucleotide variant (SNV) profiles of 28 t(14;18)-positive and 13 t(14;18)-negative FL were analyzed, followed by the integration of copy-number changes, copy-neutral LOH and published gene-expression data as well as the assessment of immunoglobulin N-glycosylation sites. Read More

    Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia.
    Leukemia 2017 Aug 18. Epub 2017 Aug 18.
    Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.
    Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Read More

    Interleukin 4 induces apoptosis of acute myeloid leukemia cells in a Stat6-dependent manner.
    Leukemia 2017 Aug 18. Epub 2017 Aug 18.
    Department of Clinical Genetics, Lund University, Lund, Sweden.
    Cytokines provide signals that regulate immature normal and acute myeloid leukemia (AML) cells in the bone marrow microenvironment. We here identify interleukin 4 (IL4) as a selective inhibitor of AML cell growth and survival in a cytokine screen using fluorescently labeled AML cells. RNA-sequencing of the AML cells revealed an IL4-induced upregulation of Stat6 target genes and enrichment of apoptosis-related gene expression signatures. Read More

    Discovery of novel drug sensitivities in T-PLL by high-throughput ex vivo drug testing and mutation profiling.
    Leukemia 2017 Aug 14. Epub 2017 Aug 14.
    Hematology Research Unit Helsinki, Department of Clinical Chemistry and Hematology, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland.
    T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells with an urgent need for rationally designed therapies to address its notoriously chemo-refractory behavior. The median survival of T-PLL patients is <2 years and clinical trials are difficult to execute. Here we systematically explored the diversity of drug responses in T-PLL patient samples using an ex vivo drug sensitivity and resistance testing platform and correlated the findings with somatic mutations and gene expression profiles. Read More

    Integrating genomic alterations in diffuse large B-cell lymphoma identifies new relevant pathways and potential therapeutic targets.
    Leukemia 2017 Aug 14. Epub 2017 Aug 14.
    Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
    Genome studies of diffuse large B-cell lymphoma (DLBCL) have revealed a large number of somatic mutations and structural alterations. However, the clinical significance of these alterations is still not well defined. In this study, we have integrated the analysis of targeted next-generation sequencing of 106 genes and genomic copy number alterations (CNA) in 150 DLBCL. Read More

    Nilotinib-induced vasculopathy: identification of vascular endothelial cells as a primary target site.
    Leukemia 2017 Nov 31;31(11):2388-2397. Epub 2017 Jul 31.
    Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
    The BCR/ABL1 inhibitor Nilotinib is increasingly used to treat patients with chronic myeloid leukemia (CML). Although otherwise well-tolerated, Nilotinib has been associated with the occurrence of progressive arterial occlusive disease (AOD). Our objective was to determine the exact frequency of AOD and examine in vitro and in vivo effects of Nilotinib and Imatinib on endothelial cells to explain AOD-development. Read More

    Enhancing venetoclax activity in acute myeloid leukemia by co-targeting MCL1.
    Leukemia 2018 Feb 28;32(2):303-312. Epub 2017 Jul 28.
    Australian Centre for Blood Diseases, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia.
    Targeted therapies are frequently combined with standard cytotoxic drugs to enhance clinical response. Targeting the B-cell lymphoma 2 (BCL-2) family of proteins is an attractive option to combat chemoresistance in leukemia. Preclinical and clinical studies indicate modest single-agent activity with selective BCL-2 inhibitors (for example, venetoclax). Read More

    Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy.
    Leukemia 2018 Feb 12;32(2):353-363. Epub 2017 Jul 12.
    Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
    In diffuse large B-cell lymphoma (DLBCL), the clinical and biological significance of concordant and discordant bone marrow (BM) involvement have not been well investigated. We evaluated 712 de novo DLBCL patients with front-line rituximab-containing treatment, including 263 patients with positive and 449 with negative BM status. Compared with negative BM disease, concordant BM adversely impacted overall and progression-free survival, independent of the International Prognostic Index (IPI) and cell-of-origin classification. Read More

    Involvement of MAF/SPP1 axis in the development of bone marrow fibrosis in PMF patients.
    Leukemia 2018 Feb 12;32(2):438-449. Epub 2017 Jul 12.
    Department of Life Sciences, Centre for Regenerative Medicine 'Stefano Ferrari', University of Modena and Reggio Emilia, Modena, Italy.
    Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hyperplastic megakaryopoiesis and myelofibrosis. We recently described the upregulation of MAF (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog) in PMF CD34+ hematopoietic progenitor cells (HPCs) compared to healthy donor. Here we demonstrated that MAF is also upregulated in PMF compared with the essential thrombocytemia (ET) and polycytemia vera (PV) HPCs. Read More

    Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status.
    Leukemia 2018 Feb 24;32(2):450-461. Epub 2017 Jul 24.
    Department of Internal Medicine-Hematology and Oncology, Faculty of Medicine, Masaryk University Brno, Czech Republic.
    The multistep process of TP53 mutation expansion during myeloproliferative neoplasm (MPN) transformation into acute myeloid leukemia (AML) has been documented retrospectively. It is currently unknown how common TP53 mutations with low variant allele frequency (VAF) are, whether they are linked to hydroxyurea (HU) cytoreduction, and what disease progression risk they carry. Using ultra-deep next-generation sequencing, we examined 254 MPN patients treated with HU, interferon alpha-2a or anagrelide and 85 untreated patients. Read More

    The T-cell leukemia-associated ribosomal RPL10 R98S mutation enhances JAK-STAT signaling.
    Leukemia 2017 Jul 24. Epub 2017 Jul 24.
    Department of Oncology, KU Leuven-University of Leuven, LKI-Leuven Cancer Institute, Leuven, Belgium.
    Several somatic ribosome defects have recently been discovered in cancer, yet their oncogenic mechanisms remain poorly understood. Here we investigated the pathogenic role of the recurrent R98S mutation in ribosomal protein L10 (RPL10 R98S) found in T-cell acute lymphoblastic leukemia (T-ALL). The JAK-STAT signaling pathway is a critical controller of cellular proliferation and survival. Read More

    Efficacy and safety of midostaurin in patients with advanced systemic mastocytosis: 10-year median follow-up of a phase II trial.
    Leukemia 2018 Feb 24;32(2):470-478. Epub 2017 Jul 24.
    Division of Hematology, Department of Medicine, Stanford University School of Medicine/Stanford Cancer Institute, Stanford, CA, USA.
    Patients with advanced systemic mastocytosis (SM) (e.g. aggressive SM (ASM), SM with an associated hematologic neoplasm (SM-AHN) and mast cell leukemia (MCL)) have limited treatment options and exhibit reduced survival. Read More

    Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity.
    Leukemia 2018 Feb 20;32(2):520-531. Epub 2017 Jul 20.
    Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX, USA.
    Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T cells against leukemia and lymphoma with promising clinical results. Extending this approach to allogeneic T cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen-specific manner without causing GVHD. Read More

    High expression of ABCG2 induced by EZH2 disruption has pivotal roles in MDS pathogenesis.
    Leukemia 2018 Feb 19;32(2):419-428. Epub 2017 Jul 19.
    Division of Cellular Therapy, Institute of Medical Science, The University of Tokyo, Minato, Tokyo, Japan.
    Both proto-oncogenic and tumor-suppressive functions have been reported for enhancer of zeste homolog 2 (EZH2). To investigate the effects of its inactivation, a mutant EZH2 lacking its catalytic domain was prepared (EZH2-dSET). In a mouse bone marrow transplant model, EZH2-dSET expression in bone marrow cells induced a myelodysplastic syndrome (MDS)-like disease in transplanted mice. Read More

    The MLL recombinome of acute leukemias in 2017.
    Leukemia 2018 Feb 13;32(2):273-284. Epub 2017 Jul 13.
    Institute of Pharmaceutical Biology/Diagnostic Center of Acute Leukemia (DCAL), Goethe-University, Frankfurt/Main, Germany.
    Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Read More

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