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https://www.readbyqxmd.com/read/28209919/clinical-significance-of-csf3r-srsf2-and-setbp1-mutations-in-chronic-neutrophilic-leukemia-and-chronic-myelomonocytic-leukemia
#1
Yuan Ouyang, Chun Qiao, Yu Chen, Su-Jiang Zhang
Chronic neutrophilic leukemia (CNL) and chronic myelomonocytic leukemia (CMML) are rare hematologic neoplasms. We performed CSF3R, SRSF2 and SETBP1 mutational analyses in 10 CNL and 56 CMML patients. In this sample cohort, 80% of CNL patients harbored CSF3R mutations, of which the CSF3R T618I mutation was dominant. Mutations in CSF3R and SETBP1 were found in 7.1% and 5.3% CMML patients respectively, while 25% of CMML patients carried SRSF2 mutations. Strikingly, we identified that all of the CSF3R mutations detected in CMML patients were represented by a P733T mutation...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209720/acquired-expression-of-cbl-q367p-in-mice-induces-dysplastic-myelopoiesis-mimicking-chronic-myelomonocytic-leukemia
#2
Yuichiro Nakata, Takeshi Ueda, Akiko Nagamachi, Norimasa Yamasaki, Ken-Ichiro Ikeda, Yasuyuki Sera, Keiyo Takubo, Akinori Kanai, Hideaki Oda, Masashi Sanada, Seishi Ogawa, Kohichiro Tsuji, Yasuhiro Ebihara, Linda Wolff, Zen-Ichiro Honda, Toshio Suda, Toshiya Inaba, Hiroaki Honda
Chronic myelomonocytic leukemia (CMML) is a hematological malignancy characterized by uncontrolled proliferation of dysplastic myelomonocytes and frequent progression to acute myeloid leukemia (AML). We identified mutations in the Cbl gene, which encodes a negative regulator of cytokine signaling, in a subset of CMML patients. To investigate the contribution of mutant Cbl in CMML pathogenesis, we generated conditional knock-in mice for Cbl that express wild-type Cbl in a steady state and inducibly express Cbl(Q367P) , a CMML-associated Cbl mutant...
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28179279/role-of-runx1-in-hematological-malignancies
#3
Raman Sood, Yasuhiko Kamikubo, Paul Liu
RUNX1 is a member of the core binding factor family of transcription factors and is indispensable for the establishment of definitive hematopoiesis in vertebrates. RUNX1 is one of the most frequently mutated genes in a variety of hematological malignancies. Germline mutations in RUNX1 cause familial platelet disorder with associated myeloid malignancies (FPDMM). Somatic mutations and chromosomal rearrangements involving RUNX1 are frequently observed in myelodysplastic syndrome (MDS) and leukemias of myeloid and lymphoid lineages, i...
February 8, 2017: Blood
https://www.readbyqxmd.com/read/28159734/monocyte-subset-analysis-accurately-distinguishes-cmml-from-mds-and-is-associated-with-a-favorable-mds-prognosis
#4
Chetasi Talati, Ling Zhang, Ghada Shaheen, Andrew Kuykendall, Markus Ball, Qing Zhang, Jeffrey E Lancet, Kenneth S Zuckerman, Alan F List, Rami Komrokji, Lynn Moscinski, Eric Padron
No abstract text is available yet for this article.
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28158286/prognostic-significance-of-setbp1-mutations-in-myelodysplastic-syndromes-chronic-myelomonocytic-leukemia-and-chronic-neutrophilic-leukemia-a-meta-analysis
#5
Li-Hong Shou, Dan Cao, Xiao-Hui Dong, Qiu Fang, Ying Wu, Yan Zhang, Ju-Ping Fei, Bao-Lian Xu
OBJECTIVES: This meta-analysis investigates the prognostic effect of SET binding protein 1 (SETBP1) mutations in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), or chronic neutrophilic leukemia (CNL). METHODS: Eligible studies from Pubmed, Embase, and Web of Science were searched from database inception through April 2016. Hazard ratios (HRs) and 95% confidence interval (CI) of overall survival (OS) were pooled to calculate the prognostic significance of SETBP1 mutation in patients...
2017: PloS One
https://www.readbyqxmd.com/read/28119224/clinical-significance-of-isolated-del-7p-in-myeloid-neoplasms
#6
Hatice Deniz Gur, Sa A Wang, Zhenya Tang, Shimin Hu, Shaoying Li, L Jeffrey Medeiros, Guilin Tang
Sole del(7p) is a rare finding in myeloid neoplasms and its clinical significance is largely unknown. Here we report 10 patients with isolated del(7p), 4 had acute myeloid leukemia (AML), 2 myelodysplastic syndromes (MDS), 1 chronic myelomonocytic leukemia (CMML), 1 primary myelofibrosis (PMF), and 2 AML in remission. Seven patients had large and 3 had small del(7p) clone. For patients with AML, 3 acquired del(7p) either at disease relapse or disease progression, then became refractory to therapy and died shortly thereafter (median 5 months)...
January 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28115276/allogeneic-hematopoietic-cell-transplant-for-adult-chronic-myelomonocytic-leukemia
#7
Hien D Liu, Kwang Woo Ahn, Zhen-Huan Hu, Mehdi Hamadani, Taiga Nishihori, Baldeep Wirk, Amer Beitinjaneh, David Rizzieri, Michael R Grunwald, Mitchell Sabloff, Richard F Olsson, Ashish Bajel, Christopher Bredeson, Andrew Daly, Yoshihiro Inamoto, Navneet Majhail, Ayman Saad, Vikas Gupta, Aaron Gerds, Adriana Malone, Martin Tallman, Ran Reshef, David I Marks, Edward Copelan, Usama Gergis, Mary Lynn Savoie, Celalettin Ustun, Mark R Litzow, Jean-Yves Cahn, Tamila Kindwall-Keller, Gorgun Akpek, Bipin N Savani, Mahmoud Aljurf, Jacob M Rowe, Peter H Wiernik, Jack W Hsu, Jorge Cortes, Matt Kalaycio, Richard Maziarz, Ronald Sobecks, Uday Popat, Edwin Alyea, Wael Saber
Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for patients with chronic myelomonocytic leukemia (CMML), however, few data exist regarding prognostic factors and transplant outcomes. We performed this retrospective study to identify prognostic factors for post-transplant outcomes. The CMML-specific prognostic scoring system (CPSS) has been validated in subjects receiving non-transplant therapy and was included in our study. From 2001-2012, there were 209 adult subjects who received HCT for CMML reported to the Center for International Blood and Marrow Transplant Research (CIBMTR)...
January 20, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28102729/chronic-myelomonocytic-leukemia-with-double-mutations-in-dnmt3a-and-flt3-itd-treated-with-decitabine-and-sorafenib
#8
Jia Gu, Zhiqiong Wang, Min Xiao, Xia Mao, Li Zhu, Ying Wang, Wei Huang
Chronic myelomonocytic leukemia (CMML) is a heterogeneous neoplastic hematologic disorder with worse overall survival. Half of CMML have mutations, but case with concomitant mutations of DNA methyltransferase 3A (DNMT3A) and Internal tandem duplications of the juxtamembrane domain of FLT3 (FLT3-ITD) in CMML was not reported before. We reported a 51-year-old man who had CMML with concomitant mutations in DNMT3A and FLT3-ITD.The patient received decitabine and sorafenib combined treatment. In this report, we reviewed DNMT3A mutation and FLT3 mutation, and we reviewed treatment of decitabine and sorafenib...
January 19, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28072764/antitumour-activity-of-trabectedin-in-myelodysplastic-myeloproliferative-neoplasms
#9
Michela Romano, Matteo Giovanni Della Porta, Anna Gallì, Nicolò Panini, Simonetta Andrea Licandro, Ezia Bello, Ilaria Craparotta, Vittorio Rosti, Elisa Bonetti, Richard Tancredi, Marianna Rossi, Laura Mannarino, Sergio Marchini, Luca Porcu, Carlos M Galmarini, Alberto Zambelli, Marco Zecca, Franco Locatelli, Mario Cazzola, Andrea Biondi, Alessandro Rambaldi, Paola Allavena, Eugenio Erba, Maurizio D'Incalci
BACKGROUND: Juvenile myelomonocytic leukaemia (JMML) and chronic myelomonocytic leukaemia (CMML) are myelodysplastic myeloproliferative (MDS/MPN) neoplasms with unfavourable prognosis and without effective chemotherapy treatment. Trabectedin is a DNA minor groove binder acting as a modulator of transcription and interfering with DNA repair mechanisms; it causes selective depletion of cells of the myelomonocytic lineage. We hypothesised that trabectedin might have an antitumour effect on MDS/MPN...
January 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28024498/-reactivated-expression-of-microrna-124-in-patients-with-myelodysplastic-syndromes-after-demethylating-therapy
#10
Yue-Sheng Meng, Song Gao, Fan-Li Hua, Ying Li
OBJECTIVE: To explore the role of microRNA-124(miR-124) in the pathogenesis of myelodysplastic syndromes(MDS) through detecting the expression level of miR-124 in bone marrow mononuclear cells(MNC) of MDS patients before and after demethylating therapy with decitabine. METHODS: The expression levels of miR-124 in the MNC of 35 MDS patients and 10 healthy donors were detected with stem-loop quantitative real time polymerase chain reaction assay. RESULTS: The expression level of miR-124 was lower in MDS patients than that in healthy donors...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27990115/urgent-coronary-artery-bypass-surgery-in-a-patient-with-postinfarction-angina-and-active-myelomonocytic-leukaemia
#11
Samuel Anthony Galea, Joseph Galea
Chronic myelomonocytic leukaemia (CMML) is a myelodysplastic/myeloproliferative neoplasm affecting the production and differentiation of the monocyte cell lineage. Cardiac surgery in the context of CMML poses challenges that are not routinely encountered. This is the first reported case in the literature of a patient with active CMML undergoing urgent on-pump coronary artery bypass grafting. A 68-year-old Caucasian man with a history of hypertension, hyperlipidaemia, hypothyroidism, and hypercholesterolaemia, who had been diagnosed by the haematologists with CMML a few months earlier but had remained untreated, underwent urgent surgical coronary revascularisation because of postinfarction angina following a non-ST elevation myocardial infarction associated with troponin I rise...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27910026/recurrent-cytogenetic-abnormalities-in-myelodysplastic-syndromes
#12
Meaghan Wall
Cytogenetic analysis has an essential role in diagnosis, classification, and prognosis of myelodysplastic syndromes (MDS). Some cytogenetic abnormalities are sufficiently characteristic of MDS to be considered MDS defining in the appropriate clinical context. MDS with isolated del(5q) is the only molecularly defined MDS subtype. The genes responsible for many aspects of 5q- syndrome, the distinct clinical phenotype associated with this condition, have now been identified. Cytogenetics forms the cornerstone of the most widely adopted prognostic scoring systems in MDS, the international prognostic scoring system (IPSS) and the revised international prognostic scoring system (IPPS-R)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27898660/asthma-and-risk-of-myelodysplastic-syndromes-a-population-based-cohort-study
#13
Henrik Frederiksen, Dóra Körmendiné Farkas, Erzsébet Horváth-Puhó, Jan M Nørgaard, Mette Nørgaard, Henrik T Sørensen
BACKGROUND: Risk factors for the development of myelodysplastic syndromes (MDS) include age, exposure to ionising radiation, and cytotoxic drug treatment. Recently, asthma also has been suggested as a risk factor for MDS. METHODS: We undertook this nationwide population-based cohort study on patients with a first-time hospital-based asthma diagnosis during 2002-2013 and followed them for the development of MDS/chronic myelomonocytic leukaemia (CMML). RESULTS: We identified 75 995 patients with incident asthma and no previous MDS/CMML diagnosis...
January 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/27881041/incidence-and-survival-outcomes-of-chronic-myelomonocytic-leukemia-in-the-united-states
#14
Guru Subramanian Guru Murthy, Ishwori Dhakal, Paulette Mehta
Chronic myelomonocytic leukemia (CMML) is an aggressive neoplasm with sparse data on outcomes at a population level. Using Surveillance Epidemiology and End Results (SEER) database, we identified 2238 patients with CMML diagnosed in the period 2003-2013. We found that the disease incidence was significantly higher with advancing age and lower in females, Blacks, and Asian/pacific islanders. Median OS declined significantly with increasing age (age 20-39 - 25 months, age 40-59 - 20 months, age 60-79 - 18 months, and age ≥80 - 11 months, p < ...
November 23, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27849645/current-management-of-patients-with-chronic-myelomonocytic-leukemia
#15
Ana Alfonso, Guillermo Montalban-Bravo, Guillermo Garcia-Manero
PURPOSE OF REVIEW: The present review will focus on the current management of patients with chronic myelomonocytic leukemia (CMML) as well as in future therapeutic perspectives. RECENT FINDINGS: CMML is a clonal hematopoietic stem cell disorder characterized by peripheral blood monocytosis and myelodysplastic and myeloproliferative alterations in the bone marrow. Clinical behavior of the disease can be heterogeneous, with some patients having an indolent form of the disease, whereas others experience an aggressive course with decreased survival and eventual transformation to leukemia...
January 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27807503/clinical-management-of-myelodysplastic-syndrome-myeloproliferative-neoplasm-overlap-syndromes
#16
Joseph A Clara, David A Sallman, Eric Padron
The myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classification, the category includes atypical chronic myeloid leukemia (aCML), chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), MDS/MPN-unclassifiable (MDS/MPN-U), and the provisional entity refractory anemia with ring sideroblasts and thrombocytosis (RARS-T). Although diagnosis currently remains based on clinicopathologic features, the incorporation of next-generation platforms has allowed for the recent molecular characterization of these diseases which has revealed unique and complex mutational profiles that support their distinct biology and is anticipated to soon play an integral role in diagnosis, prognostication, and treatment...
September 2016: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/27789175/-juvenile-myelomonocytic-leukemia-a-three-case-series
#17
I Ghariani, N Jmili-Braham, H Regaieg, B Achour, Y Ben Youssef, H Sendi, L Bakir, M Kortas
Juvenile myelomonocytic leukemia (JMML), previously known as juvenile chronic myeloid leukemia (JCML), is a rare, myelodysplastic-myeloproliferative disease typically presenting in early childhood. This disorder is difficult to distinguish from other myeloproliferative syndromes such as chronic myeloid leukemia (CML) because of the similarities in their clinical and bone marrow findings. However, because of its unique biological characteristics such as absolute monocytosis with dysplasia, absence of Philadelphia chromosome or BCR-ABL fusion protein, hypergammaglobulinemia, and raised fetal hemoglobin level, this disorder does not satisfy the criteria for inclusion in the CML or chronic myelomonocytic leukemia (CMML) group, as seen in adult patients...
December 2016: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/27781377/a-variant-c-kit-mutation-d816h-fundamental-to-the-sequential-development-of-an-ovarian-mixed-germ-cell-tumor-and-systemic-mastocytosis-with-cmml
#18
Sarah G Mitchell, Silvia T Bunting, Debra Saxe, Thomas Olson, Frank G Keller
An activating point mutation of the c-KIT tyrosine kinase receptor gene, D816H, has been described in germ cell tumors (GCTs). We report an adolescent diagnosed with an ovarian mixed GCT and systemic mastocytosis with chronic myelomonocytic leukemia (SM-CMML). The teratoma and dysgerminoma differed by copy number aberrations via single nucleotide polymorphism (SNP) microarray, but were inclusive of the same c-KIT D816H point mutation (c.2446G>C) also identified in blood and bone marrow mast cells. These findings indicate not only a clonal origin of the GCT and hematologic malignancy, but also suggest a rare KIT mutation may be playing a fundamental role in malignancy development...
October 26, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27777939/tet2-mutations-were-predictive-of-inferior-prognosis-in-the-presence-of-asxl1-mutations-in-patients-with-chronic-myelomonocytic-leukemia
#19
Yajuan Cui, Hongyan Tong, Xin Du, Bing Li, Robert Peter Gale, Tiejun Qin, Jinqin Liu, Zefeng Xu, Yue Zhang, Gang Huang, Jie Jin, Liwei Fang, Hongli Zhang, Lijuan Pan, Naibo Hu, Shiqiang Qu, Zhijian Xiao
BACKGROUND: Somatic mutations involving epigenetic regulators, histone modification and chromatin regulation, splicing components, transcription factors and signaling regulator genes are common in chronic myelomonocytic leukemia (CMML) patients. It has been consensus that ASXL1 mutations have adversely impact on overall survival (OS), while the effect of TET2 mutations remains controversial and undefined. METHODS: ASXL1 and TET2 mutations were analyzed in 141 patients with CMML using Sanger sequencing, with the aim to identify the interplay of ASXL1 and TET2 mutations in the prognosis of CMML...
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27760943/-chronic-myelomonocytic-leukemia-with-myelofibrosis-resulting-in-sudden-massive-pleural-effusion-during-cytoreductive-therapy-with-hydroxycarbamide
#20
Yoshitaka Sunami, Akihiko Gotoh, Naoki Watanabe, Yoko Edahiro, Yasuharu Hamano, Hironori Harada, Norio Komatsu
Pleural effusion may occur as a rare complication associated with myeloid hematological malignancies. However, it occasionally occurs in patients with myelodysplastic/myeloproliferative neoplasms(MDS/MPN), especially in chronic myelomonocytic leukemia(CMML)with marked leukocytosis. Pleural effusion can also develop in hematological disorders with bone marrow fibrosis. Here, we report a case of CMML with bone marrow fibrosis, in which massive pleural effusion developed rapidly during cytoreductive therapy with hydroxycarbamide(HU)...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
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