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    3102 results match your criteria Clinical Leukemia [Journal]

    1 OF 63

    A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-α in anemic patients with low-risk MDS.
    Leukemia 2018 Mar 30. Epub 2018 Mar 30.
    Medizinische Klinik und Poliklinik I, Dresden, Germany.
    Erythropoiesis-stimulating agents are first choice for treating anemia in low-risk MDS. This double-blind, placebo-controlled study assessed the efficacy and safety of epoetin-α in IPSS low- or intermediate-1 risk (i.e. Read More

    Mutation-specific signaling profiles and kinase inhibitor sensitivities of juvenile myelomonocytic leukemia revealed by induced pluripotent stem cells.
    Leukemia 2018 Jun 8. Epub 2018 Jun 8.
    Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
    Juvenile myelomonocytic leukemia (JMML) is an uncommon myeloproliferative neoplasm driven by Ras pathway mutations and hyperactive Ras/MAPK signaling. Outcomes for many children with JMML remain dismal with current standard-of-care cytoreductive chemotherapy and hematopoietic stem cell transplantation. We used patient-derived induced pluripotent stem cells (iPSCs) to characterize the signaling profiles and potential therapeutic vulnerabilities of PTPN11-mutant and CBL-mutant JMML. Read More

    Preclinical evaluation of the selective small-molecule UBA1 inhibitor, TAK-243, in acute myeloid leukemia.
    Leukemia 2018 Jun 8. Epub 2018 Jun 8.
    Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
    Acute myeloid leukemia (AML) is an aggressive hematologic malignancy for which new therapeutic approaches are required. One such potential therapeutic strategy is to target the ubiquitin-like modifier-activating enzyme 1 (UBA1), the initiating enzyme in the ubiquitylation cascade in which proteins are tagged with ubiquitin moieties to regulate their degradation or function. Here, we evaluated TAK-243, a first-in-class UBA1 inhibitor, in preclinical models of AML. Read More

    Patient-centered practice in elderly myeloma patients: an overview and consensus from the European Myeloma Network (EMN).
    Leukemia 2018 Apr 25. Epub 2018 Apr 25.
    Department of Medicine I, Hematology, Oncology & Stem Cell Transplantation, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
    Multiple myeloma is a disease typical of the elderly, and, because of the increase in life expectancy of the general population, its incidence is expected to grow in the future. Elderly patients represent a particular challenge due to their marked heterogeneity. Many new and highly effective drugs have been introduced in the last few years and results from clinical trials are promising. Read More

    NF1 mutations are recurrent in adult acute myeloid leukemia and confer poor outcome.
    Leukemia 2018 Jun 5. Epub 2018 Jun 5.
    The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
    Targeted mutation assessment of 81 genes in 1021 adults with de novo acute myeloid leukemia (AML) identified recurrent mutations in the neurofibromin 1 (NF1) gene in 52 (5.1%) patients, including 36 (5.2%) younger and 16 (4. Read More

    SRSF2 mutations drive oncogenesis by activating a global program of aberrant alternative splicing in hematopoietic cells.
    Leukemia 2018 Jun 1. Epub 2018 Jun 1.
    Section of Hematology, Department of Internal Medicine and Yale Cancer Center, Yale University School of Medicine, New Haven, CT, 06511, USA.
    Recurrent mutations in the splicing factor SRSF2 are associated with poor clinical outcomes in myelodysplastic syndromes (MDS). Their high frequency suggests these mutations drive oncogenesis, yet the molecular explanation for this process is unclear. SRSF2 mutations could directly affect pre-mRNA splicing of a vital gene product; alternatively, a whole network of gene products could be affected. Read More

    Consequences of mutant TET2 on clonality and subclonal hierarchy.
    Leukemia 2018 May 24. Epub 2018 May 24.
    Department of Translational Hematology and Oncology Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
    Somatic mutations in TET2 are common in myelodysplastic syndromes (MDS), myeloproliferative, and overlap syndromes. TET2 mutant (TET2 ) clones are also found in asymptomatic elderly individuals, a condition referred to as clonal hematopoiesis of indeterminate potential (CHIP). In various entities of TET2 neoplasia, we examined the phenotype in relation to the strata of TET2 hits within the clonal hierarchy. Read More

    Small hypoxia-primed mesenchymal stem cells attenuate graft-versus-host disease.
    Leukemia 2018 May 22. Epub 2018 May 22.
    Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.
    Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their immunosuppressive capacity. Here, we show that Small MSCs primed with Hypoxia and Calcium ions (SHC-MSCs) exhibit enhanced stemness and immunomodulatory functions for treating allogeneic conflicts. Compared with naïve cultured human umbilical cord blood-derived MSCs, SHC-MSCs were resistant to passage-dependent senescence mediated via the monocyte chemoattractant protein-1 and p53/p21 cascade and secreted large amounts of pro-angiogenic and immunomodulatory factors, resulting in suppression of T-cell proliferation. Read More

    Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups.
    Leukemia 2018 May 22. Epub 2018 May 22.
    Harvard Medical School, LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute, 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 abnormalities (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case. Read More

    A predictive model for risk of early grade ≥ 3 infection in patients with multiple myeloma not eligible for transplant: analysis of the FIRST trial.
    Leukemia 2018 Jun 26;32(6):1404-1413. Epub 2018 Apr 26.
    Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France.
    Infections are a major cause of death in patients with multiple myeloma. A post hoc analysis of the phase 3 FIRST trial was conducted to characterize treatment-emergent (TE) infections and study risk factors for TE grade ≥ 3 infection. The number of TE infections/month was highest during the first 4 months of treatment (defined as early infection). Read More

    Serial minimal residual disease (MRD) monitoring during first-line FCR treatment for CLL may direct individualized therapeutic strategies.
    Leukemia 2018 Apr 17. Epub 2018 Apr 17.
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
    Achieving undetectable MRD (U-MRD) status after chemoimmunotherapy predicts longer progression-free and overall survival. The predictive factors and timing of relapse in patients with U-MRD and value of interim MRD analysis are ill-defined. This was a prospective study of 289 patients with CLL treated first-line with FCR. Read More

    Obinutuzumab plus bendamustine in previously untreated patients with CLL: a subgroup analysis of the GREEN study.
    Leukemia 2018 Apr 27. Epub 2018 Apr 27.
    University Hospital Vall d'Hebron, Barcelona, Spain.
    GREEN (NCT01905943) is a non-randomized, open-label phase IIIb study investigating obinutuzumab alone or plus chemotherapy in chronic lymphocytic leukemia (CLL). We report a preplanned subgroup analysis of 158 previously untreated CLL patients receiving obinutuzumab-bendamustine (G-B). Patients received six 28-day cycles (C) of G-B: obinutuzumab day (D)1/D2 of C1 (25 mg D1/975 mg D2), 1000 mg D8 and D15 of C1, and D1 of C2-6; and bendamustine 70/90 mg/m D1 and D2 of C1-6. Read More

    Long intergenic non-coding RNAs have an independent impact on survival in multiple myeloma.
    Leukemia 2018 Mar 29. Epub 2018 Mar 29.
    Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, 02215, USA.
    Although long intergenic non-coding RNAs (lincRNA) role in various cancers is described, their significance in Multiple Myeloma (MM) remains poorly defined. Here we have studied the lincRNA profile and their clinical impact in MM. We performed RNA-seq on MM cells from 308 newly diagnosed and uniformly treated patients, 16 normal plasma cells and utilized RNA-seq data from 532 newly diagnosed patients from CoMMpass study to analyze for lincRNAs. Read More

    Management of patients with acute promyelocytic leukemia.
    Leukemia 2018 Jun 24;32(6):1277-1294. Epub 2018 Apr 24.
    Medical Clinic I, University Hospital Carl-Gustav-Carus, Dresden, Germany.
    With the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) acute promyelocytic leukemia (APL) has become from a detrimental to one of the most curable malignant diseases in humans. In particular, the chemotherapy-free regimen with ATO/ATRA has been proven to be highly effective in de novo APL and has become standard first-line therapy in younger adult, non-high-risk patients. Nevertheless, early death is still a major issue in APL, particularly in older patients, emphasizing the need of rapid diagnostics and supportive care together with immediate access to ATRA-based therapy. Read More

    Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network.
    Leukemia 2018 May 2. Epub 2018 May 2.
    Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
    During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the 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 drug 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

    Phase 1/2 trial of GCLAM with dose-escalated mitoxantrone for newly diagnosed AML or other high-grade myeloid neoplasms.
    Leukemia 2018 Apr 17. Epub 2018 Apr 17.
    Clinical Research Division, Fred Hutchinson Cancer Research Center/University of Washington, Seattle, WA, USA.
    Outcomes with "7 + 3" are often unsatisfactory in acute myeloid leukemia (AML). Trials demonstrating improved outcomes with high-dose cytarabine, addition of cladribine, or escalated anthracycline doses prompted a phase 1/2 study (NCT02044796) of G-CSF, cladribine, high-dose cytarabine, and dose-escalated mitoxantrone (GCLAM) in adults with newly-diagnosed AML or other high-grade myeloid neoplasms. One hundred and twenty-one patients, median age 60 (range 21-81) years, were enrolled. Read More

    Front-line therapies for elderly patients with transplant-ineligible multiple myeloma and high-risk cytogenetics in the era of novel agents.
    Leukemia 2018 Mar 28. Epub 2018 Mar 28.
    Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France.
    In multiple myeloma, certain cytogenetic abnormalities, such as t(4;14), t(14;16), and del(17p), are considered high risk and are associated with worse prognosis. Patients with these high-risk cytogenetic abnormalities, as well as those who are elderly and transplant ineligible, have not experienced the same degree of improved survival outcomes that other patients have seen with recent advances in the treatment of multiple myeloma. To date, no treatment regimen has demonstrated sustained and consistent survival benefits in elderly, transplant-ineligible patients with high-risk cytogenetic abnormalities and newly diagnosed multiple myeloma. Read More


    Minimal residual disease analysis in chronic lymphocytic leukemia: a way for achieving more personalized treatments.
    Leukemia 2018 Jun 26;32(6):1307-1316. Epub 2018 Mar 26.
    Haematological Malignancy Diagnostic Service (HMDS), Leeds Teaching Hospitals NHS Trust, Leeds and Department of Health Sciences, University of York, York, UK.
    Therapeutic approaches for chronic lymphocytic leukemia (CLL) have dramatically changed over the recent past. In parallel, quantification of minimal residual disease (MRD) proved to be an independent prognostic factor for progression-free and overall survival. The European Research Initiative on CLL (ERIC) in collaboration with American and Australasian partners developed harmonised assays that could be applied reproducibly to compare the efficacy of different treatments. Read More

    Lenalidomide enhances MOR202-dependent macrophage-mediated effector functions via the vitamin D pathway.
    Leukemia 2018 Mar 28. Epub 2018 Mar 28.
    Department of Internal Medicine 5-Hematology/Oncology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
    Macrophages are key mediators of the therapeutic effects exerted by monoclonal antibodies, such as the anti-CD38 antibody MOR202, currently introduced in multiple myeloma (MM) therapy. Therefore, it is important to understand how antibody-mediated effector functions of myeloma-associated macrophages (MAMs) are regulated. Here, we focused on the effects of vitamin D, a known regulator of macrophage effector functions. Read More

    GIPSS: genetically inspired prognostic scoring system for primary myelofibrosis.
    Leukemia 2018 Mar 23. Epub 2018 Mar 23.
    Department of Experimental and Clinical Medicine, CRIMM, Center Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy.
    International collaborations over the years have produced a series of prognostic models for primary myelofibrosis (PMF), including the recently unveiled mutation-enhanced international prognostic scoring systems for transplant-age patients (MIPSS70 and MIPSS70-plus). In the current study, we considered the feasibility of a genetically inspired prognostic scoring system (GIPSS) that is exclusively based on genetic markers. Among 641 cytogenetically annotated patients with PMF and informative for previously recognized adverse mutations, multivariable analysis identified "VHR" karyotype, "unfavorable" karyotype, absence of type 1/like CALR mutation and presence of ASXL1, SRSF2, or U2AF1Q157 mutation, as inter-independent predictors of inferior survival; the respective HRs (95% CI) were 3. Read More

    Clinical use of lentiviral vectors.
    Leukemia 2018 Mar 22. Epub 2018 Mar 22.
    Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
    Viral vectors provide an efficient means for modification of eukaryotic cells, and their use is now commonplace in academic laboratories and industry for both research and clinical gene therapy applications. Lentiviral vectors, derived from the human immunodeficiency virus, have been extensively investigated and optimized over the past two decades. Third-generation, self-inactivating lentiviral vectors have recently been used in multiple clinical trials to introduce genes into hematopoietic stem cells to correct primary immunodeficiencies and hemoglobinopathies. Read More

    RET-mediated autophagy suppression as targetable co-dependence in acute myeloid leukemia.
    Leukemia 2018 Mar 22. Epub 2018 Mar 22.
    German Cancer Consortium, Heidelberg, Germany.
    Many cases of AML are associated with mutational activation of receptor tyrosine kinases (RTKs) such as FLT3. However, RTK inhibitors have limited clinical efficacy as single agents, indicating that AML is driven by concomitant activation of different signaling molecules. We used a functional genomic approach to identify RET, encoding an RTK, as an essential gene in multiple subtypes of AML, and observed that AML cells show activation of RET signaling via ARTN/GFRA3 and NRTN/GFRA2 ligand/co-receptor complexes. Read More

    Mutation, methylation, and gene expression profiles in dup(1q)-positive pediatric B-cell precursor acute lymphoblastic leukemia.
    Leukemia 2018 Mar 12. Epub 2018 Mar 12.
    Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
    High-throughput sequencing was applied to investigate the mutation/methylation patterns on 1q and gene expression profiles in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL) with/without (w/wo) dup(1q). Sequencing of the breakpoint regions and all exons on 1q in seven dup(1q)-positive cases revealed non-synonymous somatic single nucleotide variants (SNVs) in BLZF1, FMN2, KCNT2, LCE1C, NES, and PARP1. Deep sequencing of these in a validation cohort w (n = 17)/wo (n = 94) dup(1q) revealed similar SNV frequencies in the two groups (47% vs. Read More

    The AP-1-BATF and -BATF3 module is essential for growth, survival and TH17/ILC3 skewing of anaplastic large cell lymphoma.
    Leukemia 2018 Mar 28. Epub 2018 Mar 28.
    Max-Delbrück-Center for Molecular Medicine, 13125, Berlin, Germany.
    Transcription factor AP-1 is constitutively activated and IRF4 drives growth and survival in ALK and ALK anaplastic large cell lymphoma (ALCL). Here we demonstrate high-level BATF and BATF3 expression in ALCL. Both BATFs bind classical AP-1 motifs and interact with in ALCL deregulated AP-1 factors. Read More


    Protein targeting chimeric molecules specific for bromodomain and extra-terminal motif family proteins are active against pre-clinical models of multiple myeloma.
    Leukemia 2018 Mar 27. Epub 2018 Mar 27.
    Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
    Bromodomain and extraterminal (BET) domain containing protein (BRD)-4 modulates the expression of oncogenes such as c-myc, and is a promising therapeutic target in diverse cancer types. We performed pre-clinical studies in myeloma models with bi-functional protein-targeting chimeric molecules (PROTACs) which target BRD4 and other BET family members for ubiquitination and proteasomal degradation. PROTACs potently reduced the viability of myeloma cell lines in a time-dependent and concentration-dependent manner associated with G/G arrest, reduced levels of CDKs 4 and 6, increased p21 levels, and induction of apoptosis. Read More

    Health-related quality of life in lower-risk MDS patients compared with age- and sex-matched reference populations: a European LeukemiaNet study.
    Leukemia 2018 Jun 6;32(6):1380-1392. Epub 2018 Mar 6.
    Department of Tumor Immunology - Nijmegen Center for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.
    In myelodysplastic syndromes (MDS), health-related quality of life (HRQoL) represents a relevant patient-reported outcome, which is essential in individualized therapy planning. Prospective data on HRQoL in lower-risk MDS remain rare. We assessed HRQOL by EQ-5D questionnaire at initial diagnosis in 1690 consecutive IPSS-Low/Int-1 MDS patients from the European LeukemiaNet Registry. Read More


    High-throughput sequencing of nodal marginal zone lymphomas identifies recurrent BRAF mutations.
    Leukemia 2018 Feb 28. Epub 2018 Feb 28.
    Institute of Pathology and Medical Genetics, University Hospital Basel, University of Basel, Basel, Switzerland.
    Nodal marginal zone lymphoma (NMZL) is a rare small B-cell lymphoma lacking disease-defining phenotype and precise diagnostic markers. To better understand the mutational landscape of NMZL, particularly in comparison to other nodal small B-cell lymphomas, we performed whole-exome sequencing, targeted high-throughput sequencing, and array-comparative genomic hybridization on a retrospective series. Our study identified for the first time recurrent, diagnostically useful, and potentially therapeutically relevant BRAF mutations in NMZL. Read More

    Successes and challenges in the treatment of pediatric acute myeloid leukemia: a retrospective analysis of the AML-BFM trials from 1987 to 2012.
    Leukemia 2018 Feb 22. Epub 2018 Feb 22.
    Department of Pediatric Hematology-Oncology, Pediatrics III, University Hospital of Essen, Essen, Germany.
    Overall survival (OS) of pediatric patients with acute myeloid leukemia (AML) increased in recent decades. However, it remained unknown whether advances in first-line treatment, supportive care, or second-line therapy mainly contributed to this improvement. Here, we retrospectively analyzed outcome and clinical data of 1940 pediatric AML patients (younger than 18 years of age), enrolled in the population-based AML-BFM trials between 1987 and 2012. Read More


    SAMD9 and SAMD9L in inherited predisposition to ataxia, pancytopenia, and myeloid malignancies.
    Leukemia 2018 May 25;32(5):1106-1115. Epub 2018 Feb 25.
    Department of Hematology, University Hospital Linköping, Linköping, Sweden.
    Germline mutations in the SAMD9 and SAMD9L genes, located in tandem on chromosome 7, are associated with a clinical spectrum of disorders including the MIRAGE syndrome, ataxia-pancytopenia syndrome and myelodysplasia and leukemia syndrome with monosomy 7 syndrome. Germline gain-of-function mutations increase SAMD9 or SAMD9L's normal antiproliferative effect. This causes pancytopenia and generally restricted growth and/or specific organ hypoplasia in non-hematopoietic tissues. Read More

    Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet.
    Leukemia 2018 May 27;32(5):1057-1069. Epub 2018 Feb 27.
    Center for the Study of Myelofibrosis, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
    This document updates the recommendations on the management of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs) published in 2011 by the European LeukemiaNet (ELN) consortium. Recommendations were produced by multiple-step formalized procedures of group discussion. A critical appraisal of evidence by using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology was performed in the areas where at least one randomized clinical trial was published. Read More

    Early myeloma-related death in elderly patients: development of a clinical prognostic score and evaluation of response sustainability role.
    Leukemia 2018 Feb 23. Epub 2018 Feb 23.
    Clínica Universidad de Navarra, CIMA, IDISNA, CIBERONC, Pamplona, Spain.
    Although survival of elderly myeloma patients has significantly improved there is still a subset of patients who, despite being fit and achieving optimal responses, will die within 2 years of diagnosis due to myeloma progression. The objective of this study was to define a scoring prognostic index to identify this group of patients. We have evaluated the outcome of 490 newly diagnosed elderly myeloma patients included in two Spanish trials (GEM2005-GEM2010). Read More


    Hematopoietic lineage distribution and evolutionary dynamics of clonal hematopoiesis.
    Leukemia 2018 Mar 1. Epub 2018 Mar 1.
    Department of Hematology, Oncology, and Tumor Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
    Clonal hematopoiesis of indeterminate potential (CHIP) occurs in an age-related manner and associates with an increased risk of hematologic cancer, atherosclerotic disease, and shorter overall survival. Little is known about the cell of origin, repartition patterns of clonal mutations within the hematopoietic differentiation tree, and its dynamics under evolutionary pressure. Using targeted sequencing, CHIP was identified in 121 out of 437 elderly individuals (27. Read More

    Drugging the lncRNA MALAT1 via LNA gapmeR ASO inhibits gene expression of proteasome subunits and triggers anti-multiple myeloma activity.
    Leukemia 2018 Feb 22. Epub 2018 Feb 22.
    Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy.
    The biological role and therapeutic potential of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) are still to be investigated. Here, we studied the functional significance and the druggability of the oncogenic lncRNA MALAT1 in MM. Targeting MALAT1 by novel LNA-gapmeR antisense oligonucleotide antagonized MM cell proliferation and triggered apoptosis both in vitro and in vivo in a murine xenograft model of human MM. Read More

    Hypomethylating agents in combination with immune checkpoint inhibitors in acute myeloid leukemia and myelodysplastic syndromes.
    Leukemia 2018 May 22;32(5):1094-1105. Epub 2018 Feb 22.
    Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
    Immune checkpoint inhibitors, as single-agent therapy, have shown modest clinical efficacy in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). As has been successfully shown in other less immunogenic hematologic malignancies, rationally designed combination approaches may be more effective than single-agent checkpoint inhibitors, and may be the approach to pursue in AML/MDS. Hypomethylating agents (HMAs) such as azacitidine, while enhancing anti-tumor immune response, concurrently dampen immune response by upregulating inhibitory immune checkpoint molecule expression. Read More

    Universal genetic testing for inherited susceptibility in children and adults with myelodysplastic syndrome and acute myeloid leukemia: are we there yet?
    Leukemia 2018 Feb 27. Epub 2018 Feb 27.
    Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA.
    Comprehensive genomic profiling of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) cases have enabled the detection and differentiation of driver and subclonal mutations, informed risk prognostication, and defined targeted therapies. These insights into disease biology, and management have made multigene-acquired mutation testing a critical part of the diagnostic assessment of patients with sporadic MDS and AML. More recently, our understanding of the role of an increasing number of inherited genetic factors on MDS/AML risk and management has rapidly progressed. Read More


    Persistence of pre-leukemic clones during first remission and risk of relapse in acute myeloid leukemia.
    Leukemia 2018 Feb 23. Epub 2018 Feb 23.
    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

    Pharmacologic inhibition of STAT5 in acute myeloid leukemia.
    Leukemia 2018 May 2;32(5):1135-1146. Epub 2018 Feb 2.
    Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.
    The transcription factor STAT5 is an essential downstream mediator of many tyrosine kinases (TKs), particularly in hematopoietic cancers. STAT5 is activated by FLT3-ITD, which is a constitutively active TK driving the pathogenesis of acute myeloid leukemia (AML). Since STAT5 is a critical mediator of diverse malignant properties of AML cells, direct targeting of STAT5 is of significant clinical value. Read More

    Targeting MYC in multiple myeloma.
    Leukemia 2018 Jun 22;32(6):1295-1306. Epub 2018 Feb 22.
    IRCL, INSERM UMR-S1172, Univ. Lille, Lille, France.
    Multiple myeloma (MM) is a plasma cell tumor marked by clonal evolution and preceded by a premalignant stage, which progresses via molecular pathway deregulation, including MYC activation. This activation relates to translocation or gain of the MYC locus and deregulation of upstream pathways such as IRF4, DIS3/LIN28B/let-7, or MAPK. Precision medicine is an approach to predict more accurately which treatment strategies for a particular disease will work in which groups of patients, in contrast to a "one-size-fits-all" approach. Read More

    Loss of heterozygosity as a marker of homologous repair deficiency in multiple myeloma: a role for PARP inhibition?
    Leukemia 2018 Feb 2. Epub 2018 Feb 2.
    Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
    PARP inhibitors can induce synthetic lethality in tumors characterized by homologous recombination deficiency (HRD), which can be detected by evaluating genome-wide loss of heterozygosity (LOH). Multiple myeloma (MM) is a genetically unstable tumor and we hypothesized that HRD-related LOH (HRD-LOH) could be detected in patient samples, supporting a potential role for PARP inhibition in MM. Using results from targeted next-generation sequencing studies (FoundationOne Heme), we analyzed HRD-LOH in patients at all disease stages (MGUS (n = 7), smoldering MM (SMM, n = 30), newly diagnosed MM (NDMM, n = 71), treated MM (TRMM, n = 64), and relapsed MM (RLMM, n = 234)) using an algorithm to identify HRD-LOH segments. Read More

    ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia-update on methodological approaches and results interpretation.
    Leukemia 2018 May 2;32(5):1070-1080. Epub 2018 Feb 2.
    Department of Internal Medicine - Hematology and Oncology, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.
    In chronic lymphocytic leukemia (CLL), TP53 gene defects, due to deletion of the 17p13 locus and/or mutation(s) within the TP53 gene, are associated with resistance to chemoimmunotherapy and a particularly dismal clinical outcome. On these grounds, analysis of TP53 aberrations has been incorporated into routine clinical diagnostics to improve patient stratification and optimize therapeutic decisions. The predictive implications of TP53 aberrations have increasing significance in the era of novel targeted therapies, i. Read More

    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

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