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Liting Zheng, Longyong Xu, Qing Xu, Lu Yu, Danfeng Zhao, Pu Chen, Wei Wang, Yiqin Wang, Gang Han, Charlie Degui Chen
Recurrent somatic loss-of-function mutations in histone demethylases are frequently detected in cancer. However, whether loss of a histone demethylase can cause cancer has not been determined. Here, we report that knockout of the histone demethylase Utx in mice causes a chronic myelomonocytic leukemia (CMML)-like disease with splenomegaly, monocytosis, and extramedullary hematopoiesis. Mutational analysis of patient data indicated that UTX mutations occur simultaneously with TP53 mutations in myeloid malignancies, and combined inactivation of Utx and Trp53 accelerated the development of CMML in a cell-autonomous manner...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Jill A Bell, Aaron Galaznik, Rachel Huelin, Michael Stokes, Yelan Guo, Robert J Fram, Douglas V Faller
High-dose chemotherapy with allogeneic hematopoietic stem cell transplantation (allo-HSCT) can produce long-term remission in patients with higher-risk myelodysplastic syndromes (HR-MDS) and chronic myelomonocytic leukemia (CMML). However, this treatment regimen is not appropriate for elderly and/or comorbid patients; in these cases, azacitidine is a standard treatment. This systematic review was conducted to evaluate real-world evidence of treatment options for patients with HR-MDS/CMML. Medline and Embase (January 2006 to May 2016) were searched, in addition to conference proceedings and treatment guideline reviews...
February 8, 2018: Clinical Lymphoma, Myeloma & Leukemia
D J Lewis, R N Miranda, C W Oh, T Hinojosa, L J Medeiros, J L Curry, M T Tetzlaff, C A Torres-Cabala, P Nagarajan, F Ravandi-Kashani, M Duvic
T-cell large granular lymphocytic leukaemia (T-LGLL) is a clinically indolent mature T-cell neoplasm characterized by a monoclonal population of CD3+ CD8+ cytotoxic T cells, which usually presents as neutropenia, anaemia and thrombocytopenia. Chronic myelomonocytic leukaemia (CMML) is a clonal haematopoietic disorder with features of both a myeloproliferative neoplasm and myelodysplastic syndrome (MDS). Patients with CMML exhibit a persistent peripheral blood monocytosis in addition to myelodysplastic features...
February 9, 2018: Clinical and Experimental Dermatology
Kathrin Thomay, Yvonne Lisa Behrens, Jana Lentes, Nicole Wittner, Verena Wittig, Doreen Rothe, Doris Steinemann, Brigitte Schlegelberger, Gudrun Göhring
No abstract text is available yet for this article.
January 31, 2018: Leukemia & Lymphoma
Françoise Schillinger, Elise Sourdeau, Marouane Boubaya, Lucile Baseggio, Sylvain Clauser, Edouard Cornet, Camille Debord, Jean-Pierre Defour, Frédérique Dubois, Marion Eveillard, Anne-Cécile Galoisy, Marie-Odile Geay, François Mullier, Vanessa Nivaggioni, Valérie Soenen, Pascal Morel, Francine Garnache-Ottou, Emily Ronez, Valérie Bardet, Eric Deconinck
According to WHO recommendations, diagnosis of chronic myelomonocytic leukemia (CMML) beforehand requires microscopic examination of peripheral blood to identify dysplasia and/or blasts when monocytes are greater or equal to 1.0 × 109/L and 10% of leucocytes. We analyzed parameters derived from SysmexTM XN analyzers to improve the management of microscopic examination for monocytosis. We analyzed results of the complete blood count and the positioning and dispersion parameters of polymorphonuclear neutrophils and monocytes in 61 patients presenting with CMML and 635 control patients presenting with a reactive monocytosis...
January 8, 2018: Scandinavian Journal of Clinical and Laboratory Investigation
Yanyan Zhang, Liang He, Dorothée Selimoglu-Buet, Chloe Jego, Margot Morabito, Christophe Willekens, M'boyba Khadija Diop, Patrick Gonin, Valérie Lapierre, Nathalie Droin, Eric Solary, Fawzia Louache
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder that typically associates with mutations in epigenetic, splicing, and signaling genes. Genetically modified mouse models only partially recapitulate the disease phenotype, whereas xenotransplantation of CMML cells in immunocompromised mice has been rarely successful so far. Here, CMML CD34+ cells sorted from patient bone marrow (BM) or peripheral blood (PB) were injected intravenously into NSG (NOD/LtSz-scid IL2rγnull) mice and NSG mice engineered to express human granulo-monocyte colony-stimulating factor, stem cell factor, and interleukin-3 (NSGS mice)...
June 13, 2017: Blood Advances
Zhihong Hu, Shimin Hu, Changsheng Ji, Zhenya Tang, Beenu Thakral, Sanam Loghavi, L Jeffrey Medeiros, Wei Wang
3q26.2/EVI1 rearrangements resulting in EVI1 overexpression play an important role in leukemogenesis and are associated with treatment resistance and a poorer prognosis in patients with acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia and BCR-ABL negative myeloproliferative neoplasms. In this study, we aim to explore the clinicopathological features of myelodysplastic/myeloproliferative (MDS/MPN) neoplasms with 3q26.2/EVI1 rearrangements and determine the potential impact of these cytogenetic abnormalities on treatment response and survival...
December 23, 2017: Leukemia Research
Hiroyoshi Kunimoto, Cem Meydan, Abbas Nazir, Justin Whitfield, Kaitlyn Shank, Franck Rapaport, Rebecca Maher, Elodie Pronier, Sara C Meyer, Francine E Garrett-Bakelman, Martin Tallman, Ari Melnick, Ross L Levine, Alan H Shih
Mutations in epigenetic modifiers and signaling factors often co-occur in myeloid malignancies, including TET2 and NRAS mutations. Concurrent Tet2 loss and NrasG12D expression in hematopoietic cells induced myeloid transformation, with a fully penetrant, lethal chronic myelomonocytic leukemia (CMML), which was serially transplantable. Tet2 loss and Nras mutation cooperatively led to decrease in negative regulators of mitogen-activated protein kinase (MAPK) activation, including Spry2, thereby causing synergistic activation of MAPK signaling by epigenetic silencing...
December 13, 2017: Cancer Cell
H Joachim Deeg, Emily A Stevens, Rachel B Salit, Ralph P Ermoian, Min Fang, Boglarka Gyurkocza, Mohamed L Sorror, Giancarlo Fatobene, Joachim Baumgart, Lauri M Burroughs, Colleen Delaney, Kris Doney, Daniel N Egan, Mary E D Flowers, Filippo Milano, Jerry P Radich, Bart L Scott, Eileen J Sickle, Brent L Wood, Cecilia Yeung, Barry E Storer
In this prospective randomized phase II "pick the winner" trial we assessed the efficacy of transplant conditioning with treosulfan/fludarabine ± 2 Gy total body irradiation (TBI) in reducing post-transplant relapse in 100 patients, 2-70 (median 57) years of age, with myelodysplastic syndrome/chronic myelomonocytic leukemia (MDS/CMML; n=51) or acute myeloid leukemia (AML; n=49). Patients received intravenous (IV) treosulfan, 14 g/m2/day on days -6 to -4 and IV fludarabine, 30 mg/m2/day on days -6 to -2, alone or combined with 2 Gy TBI (day 0)...
December 20, 2017: Biology of Blood and Marrow Transplantation
A H Cull, D Mahendru, B Snetsinger, D Good, K Tyryshkin, A Chesney, Z Ghorab, M Reis, R Buckstein, R A Wells, M J Rauh
Immune dysregulation is a common feature of myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML), particularly in early stages. However, the genetic basis remains poorly understood. We recently reported that macrophages from mice deficient in tet methylcytosine dioxygenase 2 (Tet2), a model of MDS/CMML, are hyperinflammatory and have increased expression of arginase 1 (Arg1). In macrophages and myeloid derived suppressor cells (MDSCs) expression of Arg1 contributes to T-cell suppression and immune evasion by L-arginine depletion, in the setting of chronic inflammation and cancer...
February 2018: Leukemia Research
Katherine Linder, Chaitanya Iragavarapu, Delong Liu
Myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndrome has been described since the 2001 WHO classification as disorders that have both proliferative and dysplastic changes simultaneously. Specific disorders include chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), BCR-ABL negative atypical chronic myeloid leukemia (aCML) and unclassifiable MDS/MPN (MPN/MDS-U). Recurrent gene mutations in these conditions have been described. Among them, SETBP1 mutations have been identified in up to 32% of aCML, 24% of JMML, 18% of CMML and 10% of MDS/MPN-U patients...
2017: Biomarker Research
E Schuler, F Frank, B Hildebrandt, B Betz, C Strupp, M Rudelius, C Aul, T Schroeder, N Gattermann, R Haas, U Germing
MDS patients may present with monocytic marrow proliferation not fulfilling criteria for CMML. We analyzed MDS patients with or without a marrow monocytic proliferation by following up the amount of monocytic proliferation and characterizing their molecular profile. 315 MDS patients of Duesseldorf MDS registry were divided into two groups: A) 183 patients with monocytic esterase positive cells in marrow and monocytes between 101 and 900/μl in blood and B) 132 patients without monocytic esterase positive cells in marrow and monocytes in blood ≤100/μl...
February 2018: Leukemia Research
Hidehiro Itonaga, Kazunari Aoki, Jun Aoki, Takayuki Ishikawa, Ken Ishiyama, Naoyuki Uchida, Toru Sakura, Kazuteru Ohashi, Mineo Kurokawa, Yukiyasu Ozawa, Ken-Ichi Matsuoka, Yukinori Nakamura, Fumihiko Kimura, Koji Iwato, Yuichiro Nawa, Makoto Hirokawa, Koji Kato, Tatsuo Ichinohe, Yoshiko Atsuta, Yasushi Miyazaki
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapeutic option for patients with chronic myelomonocytic leukemia (CMML). We retrospectively compared the post-transplantation outcomes of 159 patients with CMML who underwent allo-HSCT using 4 types of donor sources: HLA-matched related donor graft, unrelated bone marrow (U-BM), unrelated cord blood (U-CB), and HLA-mismatched related donor graft. The median patient age at allo-HSCT was 54 years (range, 16 to 75 years). In multivariate analyses, the use of HLA-matched related donor grafts correlated with better overall survival than U-BM (hazard ratio [HR], 2...
November 28, 2017: Biology of Blood and Marrow Transplantation
Laura Palomo, Roberto Malinverni, Marta Cabezón, Blanca Xicoy, Montserrat Arnan, Rosa Coll, Helena Pomares, Olga García, Francisco Fuster-Tormo, Javier Grau, Evarist Feliu, Francesc Solé, Marcus Buschbeck, Lurdes Zamora
Chromosomal abnormalities are detected in 20-30% of patients with chronic myelomonocytic leukemia (CMML) and correlate with prognosis. On the mutation level, disruptive alterations are particularly frequent in chromatin regulatory genes. However, little is known about the consequential alterations in the epigenetic marking of the genome. Here, we report the analysis of genomic DNA methylation patterns of 64 CMML patients and 10 healthy controls, using a DNA methylation microarray focused on promoter regions...
November 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
Rita Assi, Hagop M Kantarjian, Guillermo Garcia-Manero, Jorge E Cortes, Naveen Pemmaraju, Xuemei Wang, Graciela Nogueras-Gonzalez, Elias Jabbour, Prithviraj Bose, Tapan Kadia, Courtney D Dinardo, Keyur Patel, Carlos Bueso-Ramos, Lingsha Zhou, Sherry Pierce, Romany Gergis, Carla Tuttle, Gautam Borthakur, Zeev Estrov, Rajyalakshmi Luthra, Juliana Hidalgo-Lopez, Srdan Verstovsek, Naval Daver
Ruxolitinib and azacytidine target distinct disease manifestations of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPNs). Patients with MDS/MPNs initially received ruxolitinib BID (doses based on platelets count), continuously in 28-day cycles for the first 3 cycles. Azacytidine 25 mg/m2 (Day 1-5) intravenously or subcutaneously was recommended to be added to each cycle starting cycle 4 and could be increased to 75 mg/m2 (Days 1-5) for disease control. Azacytidine could be started earlier than cycle 4 and/or at higher dose in patients with rapidly proliferative disease or with elevated blasts...
February 2018: American Journal of Hematology
Meritxell Nomdedeu, Arturo Pereira, Xavier Calvo, Joan Colomer, Francesc Sole, Amparo Arias, Candida Gomez, Elisa Luño, Jose Cervera, Montserrat Arnan, Helena Pomares, Fernando Ramos, Itziar Oiartzabal, Blanca Espinet, Carme Pedro, Beatriz Arrizabalaga, María Laura Blanco, Mar Tormo, Jesus Maria Hernandez-Rivas, María Díez-Campelo, Margarita Ortega, David Valcárcel, Maria-Teresa Cedena, Rosa Collado, Javier Grau, Isabel Granada, Guillermo Sanz, Elias Campo, Jordi Esteve, Dolors Costa
Isolate loss of chromosome Y (-Y) in myelodysplastic syndromes (MDS) is associated to a better outcome but it is also well described as an age-related phenomenon. In this study we aimed to analyze the prognostic impact of -Y in the context of the IPSS-R cytogenetic classification, evaluate the clinical significance of the percentage of metaphases with isolated -Y, and test whether finding -Y may predispose to over-diagnose MDS in patients with borderline morphological features. We evaluated 3581 male patients from the Spanish MDS Registry with a diagnosis of MDS or chronic myelomonocytic leukemia (CMML)...
December 2017: Leukemia Research
Rina Chen, Enrique Y Bitchatchi
BACKGROUND: Detection and estimation of trends in cancer incidence rates are commonly achieved by fitting standardized rates to a joinpoint log-linear regression. The efficiency of this approach is inadequate when applied to a relatively low levels of incidence. We compared that approach with the Cuscore test with respect to detecting a log-linear increasing trend of chronic myelomonocytic leukemia (CMML) in datasets simulated to match a province of about 700,000 inhabitants. METHODS: For better efficiency, we replaced the standardized rate as the dependent variable with a continuous statistic that reflects the inverse of the standardized incidence ratio (SIR)...
October 2017: Cancer Epidemiology
Romain Vazquez, Mikael Roussel, Bouchra Badaoui, Nicolas Freynet, Sihem Tarfi, Eric Solary, Dorothée Selimoglu-Buet, Orianne Wagner-Ballon
BACKGROUND: Accumulation of classical monocytes CD14++ CD16- (also called MO1) ≥ 94% can accurately distinguish chronic myelomonocytic leukemia (CMML) from reactive monocytosis. The HematoFlow™ solution, able to quantify CD16 negative monocytes, could be a useful tool to manage monocytosis which remains a common issue in routine laboratories. METHODS: Classical monocytes were quantified from 153 whole blood samples collected on EDTA using both flow cytometry methods, either MO1 percentage determination by the multiparameter assay previously published and regarded here as the reference method, or CD16 negative monocyte percentage determination by the means of HematoFlow™...
November 6, 2017: Cytometry. Part B, Clinical Cytometry
Yayue Gao, Ming Gong, Chunxia Zhang, Xudong Kong, Yigai Ma
RATIONALE: Thrombocytopenia in chronic myelomonocytic leukemia (CMML) is usually attributed to impaired marrow production resulting from cytotoxic drug use or CMML itself ("CMML-induced thrombocytopenia"). In very rare cases, immune thrombocytopenia (ITP) can be a complication of CMML ("CMML-associated ITP"). However, treatment of severe thrombocytopenia in patients with CMML is still a challenge. PATIENT CONCERNS: Case 1 was a 61-year-old female patient admitted to our hospital because of skin petechiae and purpura for 6 days...
October 2017: Medicine (Baltimore)
Francesco Onida
PURPOSE OF REVIEW: Within the group of the myelodysplastic/myeloproliferative overlap neoplasms of the adult age, chronic myelomonocytic leukemia (CMML) is characterized by an extremely variable clinical course. This review aims to cover over the years main advancements in the identification of CMML clinical and biological features associated to survival outcomes and the consequent development of prognostic tools for individual patient treatment decision making. RECENT FINDINGS: According to the last WHO classification of myeloid neoplasms, three subgroups of patients may be recognized on the base of percentage of blasts in marrow and in peripheral blood (CMML-0, CMML-1, and CMML-2), with corresponding decreasing life-expectations...
December 2017: Current Hematologic Malignancy Reports
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