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    Efficacy of pegaspargase, etoposide, methotrexate and dexamethasone in newly diagnosed advanced-stage extra-nodal natural killer/T-cell lymphoma with the analysis of the prognosis of whole blood EBV-DNA.
    Blood Cancer J 2017 Sep 15;7(9):e608. Epub 2017 Sep 15.
    Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.

    High pretreatment level of soluble interleukin-2 receptor is a robust prognostic factor in patients with follicular lymphoma treated with R-CHOP-like therapy.
    Blood Cancer J 2017 Sep 29;7(9):e614. Epub 2017 Sep 29.
    Department of Hematology Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

    Meis2 as a critical player in MN1-induced leukemia.
    Blood Cancer J 2017 Sep 29;7(9):e613. Epub 2017 Sep 29.
    Terry Fox Laboratory, BC Cancer Agency Research Centre, Vancouver, British Columbia, Canada.
    Meningioma 1 (MN1) is an independent prognostic marker for normal karyotype acute myeloid leukemia (AML), with high expression linked to all-trans retinoic acid resistance and poor survival. MN1 is also a potent and sufficient oncogene in murine leukemia models, strongly dependent on the MEIS1/AbdB-like HOX protein complex to transform common myeloid progenitors, block myeloid differentiation, and promote leukemic stem cell self-renewal. To identify key genes and pathways underlying leukemic activity, we functionally assessed MN1 cell phenotypic heterogeneity, revealing leukemic and non-leukemic subsets. Read More

    High somatic mutation and neoantigen burden are correlated with decreased progression-free survival in multiple myeloma.
    Blood Cancer J 2017 Sep 22;7(9):e612. Epub 2017 Sep 22.
    Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
    Tumor-specific mutations can result in immunogenic neoantigens, both of which have been correlated with responsiveness to immune checkpoint inhibitors in highly mutagenic cancers. However, early results of single-agent checkpoint inhibitors in multiple myeloma (MM) have been underwhelming. Therefore, we sought to understand the relationship between mutation and neoantigen landscape of MM patients and responsiveness to therapies. Read More

    Understanding CD30 biology and therapeutic targeting: a historical perspective providing insight into future directions.
    Blood Cancer J 2017 Sep 8;7(9):e603. Epub 2017 Sep 8.
    Department of Haematology, Peter McCallum Cancer Centre, Melbourne, Victoria, Australia.
    CD30 is a member of the tumor necrosis factor receptor superfamily. It is characteristically expressed in certain hematopoietic malignancies, including anaplastic large cell lymphoma and Hodgkin lymphoma, among others. The variable expression of CD30 on both normal and malignant lymphoid cells has focused research efforts on understanding the pathogenesis of CD30 upregulation, its contribution to lymphomagenesis through anti-apoptotic mechanisms, and its effect on cell survival. Read More

    Secondary acute lymphoblastic leukemia is a distinct clinical entity with prognostic significance.
    Blood Cancer J 2017 Sep 8;7(9):e605. Epub 2017 Sep 8.
    Center for Oncology Hematology Outcomes Research and Training (COHORT), Division of Hematology Oncology, University of California Davis School of Medicine, Sacramento, CA, USA.
    The effect of prior malignancy on the risk of developing, and prognosis of, acute lymphoblastic leukemia (ALL) is unknown. This observational study utilized the California Cancer Registry to estimate the risk of developing ALL after a prior malignancy using standardized incidence ratios (SIRs, 95% confidence intervals). ALL occurring after a malignancy with an SIR>1 (increased-risk (IR) malignancies) was considered secondary ALL (s-ALL). Read More

    CXorf48 is a potential therapeutic target for achieving treatment-free remission in CML patients.
    Blood Cancer J 2017 Sep 1;7(9):e601. Epub 2017 Sep 1.
    Division of Clinical Physiology and Therapeutics, Keio University, Faculty of Pharmacy, Shiabakoen, Minato-ku, Tokyo, Japan.
    Although the introduction of tyrosine kinase inhibitors (TKIs) has improved overall survival of patients with chronic myeloid leukemia (CML), about half of the patients eventually relapse after cessation of TKIs. In contrast, the remainder of the patients maintain molecular remission without TKIs, indicating that the patients' immune system could control proliferation of TKI-resistant leukemic stem cells (LSCs). However, the precise mechanism of immunity against CML-LSCs is not fully understood. Read More

    Prognostic implications of abnormalities of chromosome 13 and the presence of multiple cytogenetic high-risk abnormalities in newly diagnosed multiple myeloma.
    Blood Cancer J 2017 Sep 1;7(9):e600. Epub 2017 Sep 1.
    Division of Hematology, Mayo Clinic, Rochester, MN, USA.
    Fluorescence in situ hybridization evaluation is essential for initial risk stratification in multiple myeloma. While the presence of specific cytogenetic high-risk abnormalities (HRA) is known to confer a poor prognosis, less is known about the cumulative effect of multiple HRA. We studied 1181 patients with newly diagnosed multiple myeloma who received novel agents as first-line therapy. Read More

    Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma: a study of the International Myeloma Working Group.
    Blood Cancer J 2017 Aug 25;7(8):e599. Epub 2017 Aug 25.
    Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital, Athens, Greece.
    For decades, conventional skeletal survey (CSS) has been the standard imaging technique for multiple myeloma (MM). However, recently whole-body computed tomography (WBCT) has been implemented into the diagnostic criteria of MM. This analysis compares sensitivity and prognostic significance of WBCT and CSS in patients with smoldering MM (SMM) and MM. Read More

    Alternative splicing discriminates molecular subtypes and has prognostic impact in diffuse large B-cell lymphoma.
    Blood Cancer J 2017 Aug 25;7(8):e596. Epub 2017 Aug 25.
    Research Program Unit, Medical Faculty, University of Helsinki, Helsinki, Finland.
    Effect of alternative splicing (AS) on diffuse large B-cell lymphoma (DLBCL) pathogenesis and survival has not been systematically addressed. Here, we compared differentially expressed genes and exons in association with survival after chemoimmunotherapy, and between germinal center B-cell like (GCB) and activated B-cell like (ABC) DLBCLs. Genome-wide exon array-based screen was performed from samples of 38 clinically high-risk patients who were treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis. Read More

    Vitamin D insufficiency is associated with an increased risk of early clinical failure in follicular lymphoma.
    Blood Cancer J 2017 Aug 25;7(8):e595. Epub 2017 Aug 25.
    Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
    We evaluated whether vitamin D insufficiency (VDI; 25(OH)D <20 ng/ml) was associated with adverse outcomes among follicular lymphoma (FL) patients using an observational prospective cohort study of 642 FL patients enrolled from 2002-2012. The median age at diagnosis was 60 years. At a median follow-up of 59 months, 297 patients (46%) had an event (progression, treatment failure), 78 had died and 42 (6. Read More

    Overexpression of SOX4 correlates with poor prognosis of acute myeloid leukemia and is leukemogenic in zebrafish.
    Blood Cancer J 2017 Aug 25;7(8):e593. Epub 2017 Aug 25.
    Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.
    The SOX4 transcription factor is a key regulator of embryonic development, cell-fate decision, cellular differentiation and oncogenesis. Abnormal expression of SOX4 is related to malignant tumor transformation and cancer metastasis. However, no reports are available regarding the clinical significance of SOX4 in acute myeloid leukemia (AML) and the role of SOX4 in leukemogenesis. Read More

    Revisiting gene mutations and prognosis of ex-M6a-acute erythroid leukemia with regard to the new WHO classification.
    Blood Cancer J 2017 Aug 25;7(8):e594. Epub 2017 Aug 25.
    Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille UMR1068 Inserm, Institut Paoli-Calmettes, CNRS UMR7258, Aix-Marseille Université UM105, Marseille, France.

    From Waldenström's macroglobulinemia to aggressive diffuse large B-cell lymphoma: a whole-exome analysis of abnormalities leading to transformation.
    Blood Cancer J 2017 Aug 25;7(8):e591. Epub 2017 Aug 25.
    Hematology Department, University Hospital of Salamanca and Research Biomedical Institute of Salamanca (IBSAL), Salamanca, Spain.
    Transformation of Waldenström's macroglobulinemia (WM) to diffuse large B-cell lymphoma (DLBCL) occurs in up to 10% of patients and is associated with an adverse outcome. Here we performed the first whole-exome sequencing study of WM patients who evolved to DLBCL and report the genetic alterations that may drive this process. Our results demonstrate that transformation depends on the frequency and specificity of acquired variants, rather than on the duration of its evolution. Read More

    High sensitivity blood-based M-protein detection in sCR patients with multiple myeloma.
    Blood Cancer J 2017 Aug 25;7(8):e590. Epub 2017 Aug 25.
    Protein Immunology Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
    We assessed the ability of a mass spectrometry-based technique, called monoclonal immunoglobulin rapid accurate mass measurement (miRAMM), to extend the analytical range of M-protein detection in serum samples obtained from myeloma patients in stringent complete response (sCR) post-autologous stem cell transplant (ASCT). To aid the M-protein detection post ASCT, the accurate molecular mass of the M-protein light chain at diagnosis was determined in all patients (N=30) and used to positively identify clones in the sCR serum. Day 100 post-ASCT, sCR samples had miRAMM identifiable M-proteins in 81% of patients. Read More

    Clinico-biological significance of suppressor of cytokine signaling 1 expression in acute myeloid leukemia.
    Blood Cancer J 2017 Jul 28;7(7):e588. Epub 2017 Jul 28.
    Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC.
    Suppressor of cytokine signaling 1 (SOCS1) protein, which encodes a member of signal transducers and activators of transcription-induced inhibitors, takes part in a negative regulation of cytokine signaling. The mechanism of SOCS1 in tumor carcinogenesis is complex and there have been no studies concerning the clinic-biologic implication of SOCS1 expression in acute myeloid leukemia (AML). Here, we first identified that higher bone marrow (BM) SOCS1 expression was closely associated with older age, FLT3-ITD, NPM1 and DNMT3A mutations, but negatively correlated with CEBPA mutation in patients with de novo AML. Read More

    MiR-155/miR-150 network regulates progression through the disease phases of chronic lymphocytic leukemia.
    Blood Cancer J 2017 Jul 21;7(7):e585. Epub 2017 Jul 21.
    First Internal Clinic, Department of Hematology, First Faculty of Medicine and General Hospital, Charles University, Prague, Czech Republic.

    Upregulation of TET activity with ascorbic acid induces epigenetic modulation of lymphoma cells.
    Blood Cancer J 2017 Jul 21;7(7):e587. Epub 2017 Jul 21.
    Division of Hematology, Mayo Clinic, Rochester, MN, USA.
    The Ten Eleven Translocation (TET) enzymes have been found to be mutated in both diffuse large B-cell (DLBCL) and peripheral T-cell (PTCL) lymphomas resulting in DNA hypermethylation. Recent studies in embryonal stem cells showed that ascorbic acid (AA) is a cofactor for TET with a binding site at the catalytic domain, and enhances TET activity. We hypothesized that AA could potentially enhance TET activity in lymphoma cells to cause DNA demethylation, reactivate expression of tumor suppressor genes and enhance chemosensitivity. Read More

    MYC is a positive regulator of choline metabolism and impedes mitophagy-dependent necroptosis in diffuse large B-cell lymphoma.
    Blood Cancer J 2017 Jul 7;7(7):e0. Epub 2017 Jul 7.
    State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
    The activation of oncogenes can reprogram tumor cell metabolism. Here, in diffuse large B-cell lymphoma (DLBCL), serum metabolomic analysis revealed that oncogenic MYC could induce aberrant choline metabolism by transcriptionally activating the key enzyme phosphate cytidylyltransferase 1 choline-α (PCYT1A). In B-lymphoma cells, as a consequence of PCYT1A upregulation, MYC impeded lymphoma cells undergo a mitophagy-dependent necroptosis. Read More

    Acute lymphoblastic leukemia: a comprehensive review and 2017 update.
    Blood Cancer J 2017 Jun 30;7(6):e577. Epub 2017 Jun 30.
    New York University School of Medicine, New York, USA.
    Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in differentiation and proliferation of lymphoid precursor cells. In adults, 75% of cases develop from precursors of the B-cell lineage, with the remainder of cases consisting of malignant T-cell precursors. Read More

    VEGF, VEGFR2 and GSTM1 polymorphisms in outcome of multiple myeloma patients treated with thalidomide-based regimens.
    Blood Cancer J 2017 Jun 30;7(6):e580. Epub 2017 Jun 30.
    Department of Internal Medicine, Faculty of Medical Sciences, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.

    A gene expression signature distinguishes innate response and resistance to proteasome inhibitors in multiple myeloma.
    Blood Cancer J 2017 Jun 30;7(6):e581. Epub 2017 Jun 30.
    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA.
    Extensive interindividual variation in response to chemotherapy is a major stumbling block in achieving desirable efficacy in the treatment of cancers, including multiple myeloma (MM). In this study, our goal was to develop a gene expression signature that predicts response specific to proteasome inhibitor (PI) treatment in MM. Using a well-characterized panel of human myeloma cell lines (HMCLs) representing the biological and genetic heterogeneity of MM, we created an in vitro chemosensitivity profile in response to treatment with the four PIs bortezomib, carfilzomib, ixazomib and oprozomib as single agents. Read More

    Changes in uninvolved immunoglobulins during induction therapy for newly diagnosed multiple myeloma.
    Blood Cancer J 2017 Jun 16;7(6):e569. Epub 2017 Jun 16.
    Division of Hematology, Mayo Clinic, Rochester, MN, USA.
    Little is known about the impact of multiple myeloma (MM) treatment on uninvolved immunoglobulins (Ig). We identified 448 patients who received high-dose dexamethasone (HD-DEX), lenalidomide and dexamethasone (RD), bortezomib and dexamethasone (VD), bortezomib, cyclophosphamide and dexamethasone (VCD) or bortezomib, lenalidomide and dexamethasone (VRD) for newly diagnosed MM at our institution between 2000 and 2013, and who had available data on absolute lymphocyte count (ALC) and quantitative uninvolved Ig at baseline and at the end of four cycles of therapy. Changes in ALC and uninvolved Ig were significantly different across treatments, with VCD and HD-DEX producing reductions in uninvolved Ig, and RD, VD and VRD leading to increases in uninvolved Ig. Read More

    The thrombopoietin/MPL axis is activated in the Gata1(low) mouse model of myelofibrosis and is associated with a defective RPS14 signature.
    Blood Cancer J 2017 Jun 16;7(6):e572. Epub 2017 Jun 16.
    Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, USA.
    Myelofibrosis (MF) is characterized by hyperactivation of thrombopoietin (TPO) signaling, which induces a RPS14 deficiency that de-regulates GATA1 in megakaryocytes by hampering its mRNA translation. As mice carrying the hypomorphic Gata1(low) mutation, which reduces the levels of Gata1 mRNA in megakaryocytes, develop MF, we investigated whether the TPO axis is hyperactive in this model. Gata1(low) mice contained two times more Tpo mRNA in liver and TPO in plasma than wild-type littermates. Read More

    Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib.
    Blood Cancer J 2017 Jun 16;7(6):e570. Epub 2017 Jun 16.
    Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
    Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD (n=59) or VCD (n=42) in two consecutive periods. Read More

    Systematic comparison of donor chimerism in peripheral blood and bone marrow after hematopoietic stem cell transplantation.
    Blood Cancer J 2017 Jun 2;7(6):e566. Epub 2017 Jun 2.
    Department of Internal Medicine 5 - Hematology and Oncology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen, Erlangen, Germany.

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