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    713 results match your criteria Blood Cancer Journal [Journal]

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    Leukemic stem cell signatures identify novel therapeutics targeting acute myeloid leukemia.
    Blood Cancer J 2018 Jun 6;8(6):52. Epub 2018 Jun 6.
    Department of Pediatrics, McGill University, Montreal, QC, Canada.
    Therapy for acute myeloid leukemia (AML) involves intense cytotoxic treatment and yet approximately 70% of AML are refractory to initial therapy or eventually relapse. This is at least partially driven by the chemo-resistant nature of the leukemic stem cells (LSCs) that sustain the disease, and therefore novel anti-LSC therapies could decrease relapses and improve survival. We performed in silico analysis of highly prognostic human AML LSC gene expression signatures using existing datasets of drug-gene interactions to identify compounds predicted to target LSC gene programs. Read More

    Early BCR-ABL1 decline in imatinib-treated patients with chronic myeloid leukemia: results from a multicenter study of the Chinese CML alliance.
    Blood Cancer J 2018 Jun 15;8(7):61. Epub 2018 Jun 15.
    Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
    An early molecular response is spectacularly predictive of outcome in chronic myeloid leukemia (CML) and early response landmarks may identify the high-risk patients likely to be benefit from an early therapy switch. In this study, we evaluated the most relevant cutoffs for early molecular response markers (BCR-ABL1 values at 3 months, log reduction and halving time between diagnosis and 3 months) in 476 first-line imatinib-treated Chinese patients with chronic phase CML. All outcomes were significantly superior for the 324 patients with 3-month BCR-ABL1 ≤10%, so did for the 270 patients with BCR-ABL1 >0. Read More

    Integrated DNA/RNA targeted genomic profiling of diffuse large B-cell lymphoma using a clinical assay.
    Blood Cancer J 2018 Jun 12;8(6):60. Epub 2018 Jun 12.
    Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    We sought to define the genomic landscape of diffuse large B-cell lymphoma (DLBCL) by using formalin-fixed paraffin-embedded (FFPE) biopsy specimens. We used targeted sequencing of genes altered in hematologic malignancies, including DNA coding sequence for 405 genes, noncoding sequence for 31 genes, and RNA coding sequence for 265 genes (FoundationOne-Heme). Short variants, rearrangements, and copy number alterations were determined. Read More

    Risk stratification of smoldering multiple myeloma incorporating revised IMWG diagnostic criteria.
    Blood Cancer J 2018 Jun 12;8(6):59. Epub 2018 Jun 12.
    Division of Hematology, Mayo Clinic, Rochester, MN, USA.
    In 2014, the International Myeloma Working Group reclassified patients with smoldering multiple myeloma (SMM) and bone marrow-plasma cell percentage (BMPC%) ≥ 60%, or serum free light chain ratio (FLCr) ≥ 100 or >1 focal lesion on magnetic resonance imaging as multiple myeloma (MM). Predictors of progression in patients currently classified as SMM are not known. We identified 421 patients with SMM, diagnosed between 2003 and 2015. Read More

    The Aspirin Regimens in Essential Thrombocythemia (ARES) phase II randomized trial design: Implementation of the serum thromboxane B assay as an evaluation tool of different aspirin dosing regimens in the clinical setting.
    Blood Cancer J 2018 Jun 1;8(6):49. Epub 2018 Jun 1.
    Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.
    Once-daily (od), low-dose aspirin (75-100 mg) is recommended to reduce the thrombotic risk of patients with essential thrombocytemia (ET). This practice is based on data extrapolated from other high-risk patients and an aspirin trial in polycythemia vera, with the assumption of similar aspirin pharmacodynamics in the two settings. However, the pharmacodynamics of low-dose aspirin is impaired in ET, reflecting accelerated renewal of platelet cyclooxygenase (COX)-1. Read More

    The oncogenic fusion protein CBFB-SMMHC downregulates CD48 to evade NK cell recognition.
    Blood Cancer J 2018 May 24;8(5):48. Epub 2018 May 24.
    The Lautenberg Center for General and Tumor Immunology, Department of Immunology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel.

    Myelodysplastic syndromes current treatment algorithm 2018.
    Blood Cancer J 2018 May 24;8(5):47. Epub 2018 May 24.
    Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
    Myelodysplastic syndromes (MDS) include a group of clonal myeloid neoplasms characterized by cytopenias due to ineffective hematopoiesis, abnormal blood and marrow cell morphology, and a risk of clonal evolution and progression to acute myeloid leukemia (AML). Because outcomes for patients with MDS are heterogeneous, individual risk stratification using tools such as the revised International Prognostic Scoring System (IPSS-R) is important in managing patients-including selecting candidates for allogeneic hematopoietic stem cell transplantation (ASCT), the only potentially curative therapy for MDS. The IPSS-R can be supplemented by molecular genetic testing, since certain gene mutations such as TP53 influence risk independent of established clinicopathological variables. Read More

    Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2018.
    Blood Cancer J 2018 May 23;8(5):44. Epub 2018 May 23.
    Mayo Clinic, SW Division of Hematology, 200 First Street, Rochester, MN, 55905, USA.
    Immunoglobulin light chain amyloidosis (AL) should be considered in any patient that presents to a cancer care provider with nephrotic range proteinuria, heart failure with preserved ejection fraction, non-diabetic peripheral neuropathy, unexplained hepatomegaly or diarrhea. More importantly, patients being monitored for smoldering multiple myeloma and a monoclonal gammopathy of undetermined significance (MGUS) are at risk for developing AL amyloidosis. MGUS and myeloma patients that have atypical features, including unexplained weight loss; lower extremity edema, early satiety, and dyspnea on exertion should be considered at risk for light chain amyloidosis. Read More

    Semaphorin 4D correlates with increased bone resorption, hypercalcemia, and disease stage in newly diagnosed patients with multiple myeloma.
    Blood Cancer J 2018 May 11;8(5):42. Epub 2018 May 11.
    Department of Clinical Therapeutics, Alexandra General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
    Multiple myeloma (MM) is characterized by bone destruction due to increased bone resorption and decreased bone formation. Semaphorin 4D (CD100, Sema4D) is expressed by osteoclasts, binds to its receptor Plexin-B1, and acts as a mediator of osteoclast-osteoblast interaction that ultimately inhibits osteoblastic bone formation. Preclinical data suggest that Sema4D/Plexin-B1 pathway is implicated in MM-induced bone disease. Read More

    Daratumumab, lenalidomide, and dexamethasone in East Asian patients with relapsed or refractory multiple myeloma: subgroup analyses of the phase 3 POLLUX study.
    Blood Cancer J 2018 May 1;8(4):41. Epub 2018 May 1.
    Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
    In the phase 3 POLLUX study, daratumumab plus lenalidomide and dexamethasone (DRd) significantly reduced the risk of progression/death and induced deeper responses vs. lenalidomide and dexamethasone alone (Rd) in patients with relapsed/refractory multiple myeloma (RRMM). We report a subgroup analysis of East Asian (Japanese, Korean, and Taiwanese) patients from POLLUX based on a longer follow-up of 24. Read More

    Waldenström macroglobulinemia treatment algorithm 2018.
    Blood Cancer J 2018 May 1;8(4):40. Epub 2018 May 1.
    Division of Hematology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA.
    Waldenström macroglobulinemia is often an indolent disorder, and many patients are candidates for observation with careful monitoring. For symptomatic patients, one must distinguish between those patients whose symptoms are related to immunologic manifestations associated with the IgM monoclonal protein and those that have symptoms related to progressive marrow and nodal infiltration with lymphoplasmacytic lymphoma. In Waldenström macroglobulinemia, the driver for therapy in the majority of patients is progressive anemia, secondary to bone marrow replacement by lymphoplasmacytic lymphoma. Read More

    Incorporation of mutations in five genes in the revised International Prognostic Scoring System can improve risk stratification in the patients with myelodysplastic syndrome.
    Blood Cancer J 2018 Apr 4;8(4):39. Epub 2018 Apr 4.
    Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
    Gene mutations have not yet been included in the 2016 WHO classification and revised International Prognostic Scoring System (IPSS-R), which are now widely utilized to discriminate myelodysplastic syndrome (MDS) patients regarding risk of leukemia evolution and overall survival (OS). In this study, we aimed to investigate whether integration of gene mutations with other risk factors could further improve the stratification of MDS patients. Mutational analyses of 25 genes relevant to myeloid malignancies in 426 primary MDS patients showed that mutations of CBL, IDH2, ASXL1, DNMT3A, and TP53 were independently associated with shorter survival. Read More

    A multiple myeloma-specific capture sequencing platform discovers novel translocations and frequent, risk-associated point mutations in IGLL5.
    Blood Cancer J 2018 Mar 21;8(3):35. Epub 2018 Mar 21.
    Department of Medicine, Washington University School of Medicine, St. Louis, 63110, MO, USA.
    Multiple myeloma (MM) is a disease of copy number variants (CNVs), chromosomal translocations, and single-nucleotide variants (SNVs). To enable integrative studies across these diverse mutation types, we developed a capture-based sequencing platform to detect their occurrence in 465 genes altered in MM and used it to sequence 95 primary tumor-normal pairs to a mean depth of 104×. We detected cases of hyperdiploidy (23%), deletions of 1p (8%), 6q (21%), 8p (17%), 14q (16%), 16q (22%), and 17p (4%), and amplification of 1q (19%). Read More

    Rapid, real time pathology review for ECOG/ACRIN 1412: a novel and successful paradigm for future lymphoma clinical trials in the precision medicine era.
    Blood Cancer J 2018 02 28;8(3):27. Epub 2018 Feb 28.
    Mayo Clinic, Rochester, MN, USA.
    ECOG/ACRIN 1412 (E1412) is a randomized, phase II open-label study of lenalidomide/RCHOP vs. RCHOP alone in adults with newly diagnosed de novo diffuse large B-cell lymphoma (DLBCL) and requires NanoString gene expression profiling (GEP) for cell-of-origin testing. Because of high ineligibility rate on retrospective expert central pathology review (ECPR), real-time (RT) ECPR was instituted to confirm diagnosis and ensure adequate tissue for GEP prior to study enrollment. Read More

    Defining cure in multiple myeloma: a comparative study of outcomes of young individuals with myeloma and curable hematologic malignancies.
    Blood Cancer J 2018 02 28;8(3):26. Epub 2018 Feb 28.
    Division of Hematology,, Mayo Clinic, Rochester, MN, USA.
    Advances in therapy in recent years have led investigators to challenge the dogma that multiple myeloma (MM) is incurable. We assessed overall (OS) and progression-free survival (PFS) of young patients ( ≤ 50 years) with MM and compared outcomes with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and Hodgkin lymphoma (HL). All patients ≤ 50 years with newly diagnosed MM (n = 212), FL (n = 168), DLBCL (n = 195), and HL (n = 233) between 1 January 2005 and 31 December 2015 were included. Read More

    Real-world data on prognosis and outcome of primary plasma cell leukemia in the era of novel agents: a multicenter national study by the Greek Myeloma Study Group.
    Blood Cancer J 2018 03 9;8(3):31. Epub 2018 Mar 9.
    Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
    We have studied the efficacy and the prognostic impact of novel agents in 50 primary plasma cell leukemia (pPCL) patients registered in our database. Eighty percent of patients were treated upfront with novel agent-based combinations; 40% underwent autologous stem cell transplantation (ASCT). Objective response rate was 76; 38% achieved at least very good partial response (≥vgPR) and this correlated significantly with bortezomib-based therapy plus ASCT. Read More

    Momelotinib therapy for myelofibrosis: a 7-year follow-up.
    Blood Cancer J 2018 03 7;8(3):29. Epub 2018 Mar 7.
    Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
    One-hundred Mayo Clinic patients with high/intermediate-risk myelofibrosis (MF) received momelotinib (MMB; JAK1/2 inhibitor) between 2009 and 2010, as part of a phase 1/2 trial (NCT00935987); 73% harbored JAK2 mutations, 16% CALR, 7% MPL, 44% ASXL1, and 18% SRSF2. As of July 2017, MMB was discontinued in 91% of the patients, after a median treatment duration of 1.4 years. Read More

    Detailed analysis of clonal evolution and cytogenetic evolution patterns in patients with myelodysplastic syndromes (MDS) and related myeloid disorders.
    Blood Cancer J 2018 03 7;8(3):28. Epub 2018 Mar 7.
    Department of Hematology and Medical Oncology, University Medicine Göttingen (UMG), Göttingen, Germany.
    Clonal cytogenetic evolution (CE) (i.e., acquisition of new chromosomal aberrations over time) is relevant for the progression of myelodysplastic syndromes (MDS). Read More

    Upregulation of FOXM1 in a subset of relapsed myeloma results in poor outcome.
    Blood Cancer J 2018 02 15;8(2):22. Epub 2018 Feb 15.
    Department of Pathology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, 52242, Iowa, USA.

    The small GTPase RhoU lays downstream of JAK/STAT signaling and mediates cell migration in multiple myeloma.
    Blood Cancer J 2018 02 13;8(2):20. Epub 2018 Feb 13.
    Department of Medicine, Division of Hematology, University of Padova, Padova, Italy.
    Multiple myeloma is a post-germinal center B-cell neoplasm, characterized by the proliferation of malignant bone marrow plasma cells, whose survival and proliferation is sustained by growth factors and cytokines present in the bone marrow microenvironment. Among them, IL-6 triggers the signal downstream of its receptor, leading to the activation of the JAK/STAT pathway. The atypical GTPase RhoU lays downstream of STAT3 transcription factor and could be responsible for mediating its effects on cytoskeleton dynamics. Read More

    Chronic neutrophilic leukemia: new science and new diagnostic criteria.
    Blood Cancer J 2018 02 13;8(2):19. Epub 2018 Feb 13.
    Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
    Chronic neutrophilic leukemia (CNL) is a distinct myeloproliferative neoplasm defined by persistent, predominantly mature neutrophil proliferation, marrow granulocyte hyperplasia, and frequent splenomegaly. The seminal discovery of oncogenic driver mutations in CSF3R in the majority of patients with CNL in 2013 generated a new scientific framework for this disease as it deepened our understanding of its molecular pathogenesis, provided a biomarker for diagnosis, and rationalized management using novel targeted therapies. Consequently, in 2016, the World Health Organization (WHO) revised the diagnostic criteria for CNL to reflect such changes in its genomic landscape, now including the presence of disease-defining activating CSF3R mutations as a key diagnostic component of CNL. Read More

    The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion.
    Blood Cancer J 2018 02 9;8(2):15. Epub 2018 Feb 9.
    Mayo Clinic, Rochester, MN, USA.
    The new edition of the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues was published in September 2017. Under the category of myeloproliferative neoplasms (MPNs), the revised document includes seven subcategories: chronic myeloid leukemia, chronic neutrophilic leukemia, polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), chronic eosinophilic leukemia-not otherwise specified and MPN, unclassifiable (MPN-U); of note, mastocytosis is no longer classified under the MPN category. In the current review, we focus on the diagnostic criteria for JAK2/CALR/MPL mutation-related MPNs: PV, ET, and PMF. Read More

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