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https://www.readbyqxmd.com/read/28370365/monocytosis-in-polycythemia-vera-clinical-and-molecular-correlates
#1
Daniela Barraco, Sonia Cerquozzi, Naseema Gangat, Mrinal M Patnaik, Terra Lasho, Christy Finke, Curtis A Hanson, Rhett P Ketterling, Animesh Pardanani, Ayalew Tefferi
Monocytosis (absolute monocyte count, AMC ≥1 x 10(9) /L) might accompany a spectrum of myeloid neoplasms, other than chronic myelomonocytic leukemia (CMML). In the current study, we examined the prevalence, laboratory and molecular correlates, and prognostic relevance of monocytosis in polycythemia vera (PV). Among 267 consecutive patients with World Health Organization (WHO)-defined PV, 55 (21%) patients displayed an AMC of ≥1 x 10(9) /L and 18 (7%) an AMC of ≥1.5 x 10(9) /L. In general, PV patients with monocytosis were significantly older and displayed higher frequencies of leukocytosis (81% vs 50% at AMC ≥1 x 10(9) /L) and TET2/SRSF2 mutations (57%/29% vs 19%/1% at AMC≥1...
March 28, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28370097/natural-history-of-chronic-myelomonocytic-leukemia-treated-with-hypomethylating-agents
#2
Ana Alfonso, Guillermo Montalban-Bravo, Koichi Takahashi, Elias J Jabbour, Tapan Kadia, Farhad Ravandi, Jorge Cortes, Zeev Estrov, Gautam Borthakur, Naveen Pemmaraju, Marina Konopleva, Carlos Bueso-Ramos, Sherry Pierce, Hagop Kantarjian, Guillermo Garcia-Manero
Hypomethylating agents (HMA) are the most commonly used therapeutic intervention in chronic myelomonocytic leukemia (CMML). Due to the lack of CMML-specific clinical trials, the impact of these agents in the natural history of CMML is not fully understood. We present the largest retrospective series of CMML (n=151) treated with HMA. Mean age at diagnosis was 69 years (range 50-88). According to the CMML-specific prognostic scoring system (CPSS): 17 (15%) were low-risk, 45 (39%) intermediate-1 risk, 42 (36%) intermediate-2, and 12 (10%) high-risk...
March 28, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28368509/in-higher-risk-myelodysplastic-syndromes-and-low-blast-count-acute-myeloid-leukemia-results-of-the-bmt-aza-prospective-study
#3
M T Voso, G Leone, A Piciocchi, L Fianchi, S Santarone, A Candoni, M Criscuolo, A Masciulli, E Cerqui, A Molteni, C Finelli, M Parma, A Poloni, A M Carella, F Spina, A Cortelezzi, F Salvi, E P Alessandrino, A Rambaldi, S Sica
Background: Allogeneic stem cell transplantation (HSCT) is the only curative treatment in myelodysplastic syndromes (MDS). Azacitidine (AZA) is increasingly used prior to HSCT, however in Europe it is only approved for patients who are not eligible for HSCT. Patients and Methods: We conducted a phase II multicenter study to prospectively evaluate the feasibility of HSCT after treatment with AZA in 70 patients with a myelodysplastic syndrome (MDS), 19 with acute myeloid leukemia (AML), and 8 with chronic myelomonocytic leukemia (CMML)...
March 29, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28360359/the-classical-nature-of-distinctive-cmml-monocytes
#4
Peter L Greenberg
No abstract text is available yet for this article.
March 30, 2017: Blood
https://www.readbyqxmd.com/read/28359286/the-double-edged-sword-of-re-expression-of-genes-by-hypomethylating-agents-from-viral-mimicry-to-exploitation-as-priming-agents-for-targeted-immune-checkpoint-modulation
#5
REVIEW
Florian Wolff, Michael Leisch, Richard Greil, Angela Risch, Lisa Pleyer
Hypomethylating agents (HMAs) have been widely used over the last decade, approved for use in myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). The proposed central mechanism of action of HMAs, is the reversal of aberrant methylation in tumor cells, thus reactivating CpG-island promoters and leading to (re)expression of tumor suppressor genes. Recent investigations into the mode of action of azacitidine (AZA) and decitabine (DAC) have revealed new molecular mechanisms that impinge on tumor immunity via induction of an interferon response, through activation of endogenous retroviral elements (ERVs) that are normally epigenetically silenced...
March 31, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28292946/nox2-dependent-immunosuppression-in-chronic-myelomonocytic-leukemia
#6
Johan Aurelius, Alexander Hallner, Olle Werlenius, Rebecca Riise, Lars Möllgård, Mats Brune, Markus Hansson, Anna Martner, Fredrik B Thorén, Kristoffer Hellstrand
Chronic myelomonocytic leukemia (CMML) is a myeloproliferative and myelodysplastic neoplasm with few treatment options and dismal prognosis. The role of natural killer (NK) cells and other antileukemic lymphocytes in CMML is largely unknown. We aimed to provide insight into the mechanisms of immune evasion in CMML with a focus on immunosuppressive reactive oxygen species (ROS) formed by the myeloid cell NADPH oxidase-2 (NOX2). The dominant population of primary human CMML cells was found to express membrane-bound NOX2 and to release ROS, which, in turn, triggered extensive PARP-1-dependent cell death in cocultured NK cells, CD8(+) T effector memory cells, and CD8(+) T effector cells...
March 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28275539/a-case-of-acute-myeloid-leukemia-with-e6a2-bcr-abl-fusion-transcript-acquired-after-progressing-from-chronic-myelomonocytic-leukemia
#7
Jinjuan Yao, Dan Douer, Lu Wang, Maria E Arcila, Khedoudja Nafa, April Chiu
Philadelphia (Ph) chromosome is a cytogenetic hallmark of chronic myeloid leukemia (CML). Most patients with CML harbor either the e13a2 or e14a2 BCR-ABL fusion product, while a small subset of the cases expresses e1a2 or e19a2 transcripts. We report a patient with chronic myelomonocytic leukemia (CMML), initially Ph chromosome negative at presentation, with rapid disease progression to acute myeloid leukemia (AML) and appearance of Ph chromosome and BCR-ABL e6a2, a very uncommon fusion transcript. The AML was refractory to treatment with subsequent emergence and dominance of a Ph negative leukemic clone...
2017: Leukemia Research Reports
https://www.readbyqxmd.com/read/28274536/chronic-myelomonocytic-leukemia-blast-crisis-in-a-patient-with-advanced-non-small-cell-lung-cancer-treated-with-egfr-tyrosine-kinase-inhibitors
#8
Hiroaki Ogata, Isamu Okamoto, Goichi Yoshimoto, Teppei Obara, Kayo Ijichi, Eiji Iwama, Taishi Harada, Koichi Akashi, Yoichi Nakanishi
A 59-year-old woman with epidermal growth factor receptor gene (EGFR) mutation-positive advanced lung adenocarcinoma was treated with afatinib after a diagnosis of chronic myelomonocytic leukemia (CMML). Twenty-one weeks later, she developed agranulocytosis, and CMML subsequently progressed to blast crisis. After complete remission of CMML, gefitinib was initiated; however, agranulocytosis recurred. This is the first reported case of both EGFR mutation-positive advanced non-small cell lung cancer with CMML, and of CMML blast crisis...
March 2017: Respiratory Investigation
https://www.readbyqxmd.com/read/28209919/clinical-significance-of-csf3r-srsf2-and-setbp1-mutations-in-chronic-neutrophilic-leukemia-and-chronic-myelomonocytic-leukemia
#9
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...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209720/acquired-expression-of-cbl-q367p-in-mice-induces-dysplastic-myelopoiesis-mimicking-chronic-myelomonocytic-leukemia
#10
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
#11
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
#12
LETTER
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.
March 30, 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
#13
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
#14
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-transplantation-for-adult-chronic-myelomonocytic-leukemia
#15
Hien Duong 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 transplantation outcomes. We performed this retrospective study to identify prognostic factors for post-transplantation outcomes. The CMML-specific prognostic scoring system (CPSS) has been validated in subjects receiving nontransplantation therapy and was included in our study. From 2001 to 2012, 209 adult subjects who received HCT for CMML were reported to the Center for International Blood and Marrow Transplant Research...
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
#16
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
#17
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
#18
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
#19
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
#20
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
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