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Myelodysplastic syndromes

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https://www.readbyqxmd.com/read/28634182/sf3b1-initiating-mutations-in-mds-with-ring-sideroblasts-target-lymphomyeloid-hematopoietic-stem-cells
#1
Teresa Mortera-Blanco, Marios Dimitriou, Petter S Woll, Mohsen Karimi, Edda Elvarsdottir, Simona Conte, Magnus Tobiasson, Monika Jansson, Iyadh Douagi, Matahi Moarii, Leonie Saft, Elli Papaemmanuil, Sten Eirik W Jacobsen, Eva Hellström-Lindberg
Mutations in the RNA splicing gene SF3B1 are found in more than 80% of patients with myelodysplastic syndrome with ring sideroblasts (MDS-RS). We investigated the origin of SF3B1 mutations within the bone marrow hematopoietic stem and progenitor cell compartments in patients with MDS-RS. Screening for recurrently mutated genes in the mononuclear cell fraction revealed mutations in SF3B1 in 39 of 40 cases (97.5%), combined with TET2 and DNMT3A in 11 (28%) and 6 (15%) patients, respectively. All recurrent mutations identified in mononuclear cells could be tracked back to the phenotypically defined hematopoietic stem cell (HSC) compartment in all investigated patients, and were also present in downstream myeloid and erythroid progenitor cells...
June 20, 2017: Blood
https://www.readbyqxmd.com/read/28631944/clinical-significance-of-repeat-blood-cultures-during-febrile-neutropenia-in-adult-acute-myeloid-leukaemia-patients-undergoing-intensive-chemotherapy
#2
Shun-Ichi Kimura, Ayumi Gomyo, Jin Hayakawa, Masaharu Tamaki, Yu Akahoshi, Naonori Harada, Tomotaka Ugai, Machiko Kusuda, Kazuaki Kameda, Hidenori Wada, Yuko Ishihara, Koji Kawamura, Kana Sakamoto, Miki Sato, Kiriko Terasako-Saito, Misato Kikuchi, Hideki Nakasone, Shinichi Kako, Aki Tanihara, Yoshinobu Kanda
BACKGROUND: We evaluated the clinical significance of repeat blood cultures in persistent and recurrent fever during neutropenia in adult acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients undergoing intensive chemotherapy. METHODS: We retrospectively reviewed the chemotherapy cycles at our centre between January 2007 and December 2015. Blood cultures obtained within three days after initial febrile neutropenia (FN) were defined as initial blood cultures and those obtained on or after day 4 were defined as repeat blood cultures...
June 20, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28630119/gata2-haploinsufficiency-accelerates-evi1-driven-leukemogenesis
#3
Saori Katayama, Mikiko Suzuki, Ayaka Yamaoka, Nadine Keleku-Lukwete, Fumiki Katsuoka, Akihito Otsuki, Shigeo Kure, James Douglas Engel, Masayuki Yamamoto
Chromosomal rearrangements between 3q21 and 3q26 induce inappropriate EVI1 expression by recruiting a GATA2-distal hematopoietic enhancer (G2DHE) to the proximity of the EVI1 gene, leading to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The acquisition of G2DHE by the EVI1 gene reciprocally deprives this enhancer of one of the two GATA2 alleles, resulting in a loss of function genetic reduction in GATA2 abundance. As GATA2 haploinsufficiency is strongly associated with MDS and AML, here we asked whether EVI1 misexpression and GATA2 haploinsufficiency both contributed to the observed leukemogenesis by using a 3q21q26 mouse model that recapitulates the G2DHE-driven EVI1 misexpression but in this case coupled to a Gata2 heterozygous germ-line deletion...
June 19, 2017: Blood
https://www.readbyqxmd.com/read/28627644/5%C3%A2-aza%C3%A2-2-%C3%A2-deoxycytidine-promotes-migration-of-acute-monocytic-leukemia-cells-via-activation-of-ccl2%C3%A2-ccr2%C3%A2-erk-signaling-pathway
#4
Xia Xiao, Qian Xu, Yan Sun, Ziwei Lu, Rui Li, Xinxin Wang, Xin Jiang, Guirong Zhang, Yechen Xiao
5-aza‑2'-deoxycytidine (5-Aza) has been approved for clinical use in the treatment of myelodysplastic syndrome and acute myeloid leukemia (AML). It inhibits cell proliferation and induces cell differentiation by demethylating various genes, including tumor suppressor genes, transcription factors, and genes encoding cell cycle inhibitors. Although it has demonstrated efficacy in the clinic, drug resistance following 5‑Aza treatment occurs. Cell migration and invasion following 5‑Aza treatment are considered to be the key factors underlying drug resistance; however, there is currently limited information regarding the detailed mechanisms involved...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28626220/a-phase-3-randomized-placebo-controlled-trial-of-darbepoetin-alfa-in-patients-with-anemia-and-lower-risk-myelodysplastic-syndromes
#5
U Platzbecker, A Symeonidis, E N Oliva, J S Goede, M Delforge, J Mayer, B Slama, S Badre, E Gasal, B Mehta, J Franklin
Use of darbepoetin alfa to treat anemia in patients with lower-risk myelodysplastic syndromes (MDS) was evaluated in a phase 3 trial. Eligible patients had low/intermediate-1 risk MDS, hemoglobin ⩽10 g/dl, low transfusion burden, and serum erythropoietin ⩽500 mU/ml. Patients were randomized 2:1 to receive 24 weeks of subcutaneous darbepoetin alfa 500 μg or placebo every 3 weeks (Q3W), followed by 48 weeks of open-label darbepoetin alfa. A total of 147 patients were randomized, with median hemoglobin of 9...
June 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28625017/a-single-tube-flow-cytometric-procedure-for-enhancing-the-diagnosis-and-prognostic-classification-of-patients-with-myelodysplastic-syndromes
#6
B Kárai, J Bedekovics, Zs Miltényi, L Gergely, L Szerafin, A Ujfalusi, J Kappelmayer, Zs Hevessy
INTRODUCTION: We created a simple and effective flow cytometry scoring system (FCSS) for suspected Myelodysplastic syndromes (MDS) samples and evaluated its diagnostic and prognostic potential. METHODS: Besides evaluating the four parameters suggested by Ogata, we investigated erythroid precursors and mast cells. We evaluated the six-parameter FCSS in a four-color setting (test cohort: 51 patients; 25 controls), then we implemented it into an eight-color setting and tested it on a validation cohort of patients with MDS (n=31)...
June 18, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28624804/can-we-consider-discontinuation-of-hypomethylating-agents-in-patients-with-myelodysplastic-syndrome-a-retrospective-study-from-the-korean-society-of-hematology-aml-mds-working-party
#7
Da Jung Kim, Ho Sup Lee, Joon-Ho Moon, Sang Kyun Sohn, Hyeoung Joon Kim, June-Won Cheong, Deog-Yeon Jo, Hawk Kim, Hyewon Lee, Soo-Mee Bang, Won Sik Lee, Yong Park, Mark Hong Lee, Jae Hoon Lee, Sung Hwa Bae, Min Kyoung Kim
It is often difficult to continue treatment with hypomethylating agent(HMA) in clinical practice because of problems such as toxicities, poor economics, etc. We compared clinical outcomes of those patients who continued HMA and those who discontinued HMA because of other causes, and evaluated factors associated with survival in those patients who discontinued HMA.Patients were divided into two groups: treatment failure, those who stopped treatment due to disease progression; and discontinuation, those who discontinued treatment because of other causes...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28622367/role-of-serum-ferritin-level-on-overall-survival-in-patients-with-myelodysplastic-syndromes-results-of-a-meta-analysis-of-observational-studies
#8
Claudia Pileggi, Maddalena Di Sanzo, Valentina Mascaro, Maria Grazia Marafioti, Francesco Saverio Costanzo, Maria Pavia
BACKGROUND: The role of serum ferritin (SF) as a prognostic factor has been analyzed in patients with myelodysplastic syndromes (MDS) who have undergone hematopoietic stem cell transplantation (HSCT), but the prognostic role of elevated SF levels is still controversial in lower risk MDS patients. Therefore, we performed a meta-analysis of all available published literature to evaluate whether elevated SF levels are associated with a worse overall survival (OS) among patients with low risk MDS...
2017: PloS One
https://www.readbyqxmd.com/read/28618451/multicenter-comparison-of-cd34-myeloid-cell-count-by-flow-cytometry-in-low-risk-myelodysplastic-syndrome-is-it-feasible
#9
Patricia Font, Dolores Subirá, Sergio Matarraz, Celina Benavente, María Teresa Cedena, Marta Morado, Ana Pérez Corral, José María Bellón, José Luis Díez-Martín
BACKGROUND: Accuracy of bone marrow (BM) blast count in low-risk myelodysplastic syndromes (MDS) still remains a challenge though it is essential for prognosis. We investigated whether the enumeration of CD34+ myeloid cells by flow cytometry immunophenotyping (FCI) could be used as a consistent parameter for clinical MDS studies. METHODS: Six clinical centres entered the study and information on their FCI protocols was recorded. Sixty-seven flow cytometry listmodes from BM samples of patients with low-risk MDS with <5% BM blasts were exchanged among participants in two different rounds...
June 15, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28616874/romiplostim-monotherapy-in-thrombocytopenic-patients-with-myelodysplastic-syndromes-long-term-safety-and-efficacy
#10
Pierre Fenaux, Petra Muus, Hagop Kantarjian, Roger M Lyons, Richard A Larson, Mikkael A Sekeres, Pamela S Becker, Amelia Orejudos, Janet Franklin
Romiplostim can improve platelet counts in about 50% of patients with low- or intermediate 1-risk (lower risk) myelodysplastic syndromes (MDS) and thrombocytopenia, but its long-term toxicity and efficacy are not known. This open-label extension study evaluated the long-term safety and efficacy of romiplostim in 60 patients with lower risk MDS and platelet counts ≤50 × 10(9) /l. The primary endpoint was adverse event (AE) incidence. Secondary endpoints were efficacy parameters, including bleeding events and platelet response...
June 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28614552/histiocytoid-sweet-syndrome-and-myelodysplastic-syndrome-reply
#11
Victoria Alegría-Landa, Lorenzo Cerroni, Luis Requena
No abstract text is available yet for this article.
June 14, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28614548/histiocytoid-sweet-syndrome-and-myelodysplastic-syndrome
#12
Marie Dominique Vignon-Pennamen, Amélie Osio, Maxime Battistella
No abstract text is available yet for this article.
June 14, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28614398/5-aza-2-deoxycytidine-in-the-medial-prefrontal-cortex-regulates-alcohol-related-behavior-and-ntf3-trkc-expression-in-rats
#13
Xiaomeng Qiao, Fangyuan Yin, Yuanyuan Ji, Yunxiao Li, Peng Yan, Jianghua Lai
Recent studies have indicated that DNA methylation plays an important role in the development of alcohol abuse. 5-Aza-2'-deoxycytidine (5-Aza-dc), an inhibitor of DNA methyltransferases, was FDA approved for myelodysplastic syndrome treatment. However, it is unclear whether 5-Aza-dc is involved in alcohol abuse. In this study, using a chronic alcohol exposure model in rats, 5-Aza-dc was injected into the medial prefrontal cortex (mPFC). Alcohol-drinking behavior and the anxiety related behavior were evaluated by two-bottle choice and open field test...
2017: PloS One
https://www.readbyqxmd.com/read/28612357/multidimensional-assessment-of-patient-condition-and-mutational-analysis-in-peripheral-blood-as-tools-to-improve-outcome-prediction-in-myelodysplastic-syndromes-a-prospective-study-of-the-spanish-mds-group
#14
Fernando Ramos, Cristina Robledo, Arturo Pereira, Carmen Pedro, Rocío Benito, Raquel de Paz, Mónica Del Rey, Andrés Insunza, Mar Tormo, María Díez-Campelo, Blanca Xicoy, Eduardo Salido, Javier Sánchez-Del-Real, Leonor Arenillas, Lourdes Florensa, Elisa Luño, Consuelo Del Cañizo, Guillermo F Sanz, Jesús María Hernández-Rivas
The International Prognostic Scoring System and its revised form (IPSS-R) are the most widely used indices for prognostic assessment of patients with myelodysplastic syndromes (MDS), but can only partially account for the observed variation in patient outcomes. This study aimed to evaluate the relative contribution of patient condition and mutational status in peripheral blood when added to the IPSS-R, for estimating overall survival and the risk of leukemic transformation in patients with MDS. A prospective cohort (2006-2015) of 200 consecutive patients with MDS were included in the study series and categorized according to the IPSS-R...
June 13, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28612220/individual-outcome-prediction-for-myelodysplastic-syndrome-mds-and-secondary-acute-myeloid-leukemia-from-mds-after-allogeneic-hematopoietic-cell-transplantation
#15
Michael Heuser, Razif Gabdoulline, Patrick Löffeld, Vera Dobbernack, Henriette Kreimeyer, Mira Pankratz, Madita Flintrop, Alessandro Liebich, Sabrina Klesse, Victoria Panagiota, Michael Stadler, Martin Wichmann, Rabia Shahswar, Uwe Platzbecker, Christian Thiede, Thomas Schroeder, Guido Kobbe, Robert Geffers, Brigitte Schlegelberger, Gudrun Göhring, Hans-Heinrich Kreipe, Ulrich Germing, Arnold Ganser, Nicolaus Kröger, Christian Koenecke, Felicitas Thol
We integrated molecular data with available prognostic factors in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML) from MDS to evaluate their impact on prognosis. Three hundred four patients were sequenced for mutations in 54 genes. We used a Cox multivariate model and competing risk analysis with internal and cross validation to identify factors prognostic of overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM)...
June 13, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28611040/%C3%AE-catenin-is-a-candidate-therapeutic-target-for-myeloid-neoplasms-with-del-5q
#16
Liping Li, Yue Sheng, Wenshu Li, Chao Hu, Nupur Mittal, Kaoru Tohyama, Amber Seba, Youyang Zhao, Howard Ozer, Tongyu Zhu, Zhijian Qian
Deletion of the chromosome 5q [del(5q)] is one of the most common cytogenetic abnormalities observed in patients with de novo myelodysplastic syndromes (MDS) and therapy-related MDS or acute myeloid leukemia (t-MDS/tAML). Emerging evidence indicates that activation of the Wnt/β-catenin pathway contributes to the development of myeloid neoplasms with del(5q). Whether β-catenin is a potential therapeutic target for myeloid neoplasms with del(5q) has yet to be evaluated. Here we report that genetic deletion of a single allele of β-catenin rescues ineffective hematopoiesis in an Apc haploinsufficient mouse model, which recapitulates several characteristic features of the pre-leukemic stage of myeloid neoplasms with a -5/del(5q)...
June 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28603827/prognostic-factors-predicting-overall-survival-in-moroccan-patients-with-myelodysplastic-syndrome
#17
Selim Jennane, Sanae Amelal, Mahtat El Mehdi, Samir Ahid, Nezha Messaoudi, Kamal Doghmi, Mohammed Mikdame
BACKGROUND: Prognostic scores are an indispensable tool in the management of myelodysplastic syndromes. AIM: Identify prognostic factors influencing overall survival of patients with myelodysplastic syndromes. METHODS: We included all patients with myelodysplastic syndromes treated in the clinical hematology department of the military hospital of Rabat (Morocco). RESULTS: Seventy-four patients were included. The sex ratio [M / F] was 1...
August 2016: La Tunisie Médicale
https://www.readbyqxmd.com/read/28601896/influence-of-tnf-and-il6-gene-polymorphisms-on-the-severity-of-cytopenias-in-argentine-patients-with-myelodysplastic-syndromes
#18
Yesica Bestach, Virginia Palau Nagore, María G Flores, Jacqueline González, Jorge Arbelbide, Nora Watman, Yamila Sieza, Irene Larripa, Carolina Belli
Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematologic disorders characterized by cytopenia(s) and predisposition to leukemic progression. An immune dysregulation and an aberrant bone marrow microenvironment seem to be key elements in the physiopathological process of MDS. In order to evaluate a possible association between susceptibility and clinic-pathologic features, we genotyped 153 MDS patients for functional cytokine polymorphisms: TNF (-308 G/A), IFNG (+874 A/T and +875 CAn), IL6 (-174 G/C), and TGFB1 (+869 C/T and +915 G/C)...
June 10, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28600665/determination-of-degradation-kinetics-and-effect-of-anion-exchange-resin-on-dissolution-of-novel-anticancer-drug-rigosertib-in-acidic-conditions
#19
Hardikkumar H Patel, Manoj Maniar, Chen Ren, Rutesh H Dave
Rigosertib is a novel anticancer drug in clinical development by Onconova therapeutics, Inc. Currently, it is in pivotal phase III clinical trials for myelodysplastic syndrome (MDS) patients. Chemically, it is a sodium salt of weak acid with low solubility in lower pH solutions. In the preliminary studies, it was found that rigosertib is unstable in acidic conditions and forms multiple degradation products. In this research, drug degradation kinetics of rigosertib were studied in acidic conditions. Rigosertib follows pseudo-first-order general acid catalysis reaction...
June 9, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28600436/accurate-quantification-of-chromosomal-lesions-via-short-tandem-repeat-analysis-using-minimal-amounts-of-dna
#20
Johann-Christoph Jann, Daniel Nowak, Florian Nolte, Stephanie Fey, Verena Nowak, Julia Obländer, Jovita Pressler, Iris Palme, Christina Xanthopoulos, Alice Fabarius, Uwe Platzbecker, Aristoteles Giagounidis, Katharina Götze, Anne Letsch, Detlef Haase, Richard Schlenk, Gesine Bug, Michael Lübbert, Arnold Ganser, Ulrich Germing, Claudia Haferlach, Wolf-Karsten Hofmann, Maximilian Mossner
BACKGROUND: Cytogenetic aberrations such as deletion of chromosome 5q (del(5q)) represent key elements in routine clinical diagnostics of haematological malignancies. Currently established methods such as metaphase cytogenetics, FISH or array-based approaches have limitations due to their dependency on viable cells, high costs or semi-quantitative nature. Importantly, they cannot be used on low abundance DNA. We therefore aimed to establish a robust and quantitative technique that overcomes these shortcomings...
June 9, 2017: Journal of Medical Genetics
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