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leukemia myelomonocytic

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
Kenneth G Liu, Amit Verma, Olga Derman, Noah Kornblum, Murali Janakiram, Ira Braunschweig, Ramakrishna Battini
BACKGROUND: Population studies showed that patients with JAK2 V617F mutation had increased mortality, and increased risk of any cancer, hematologic cancer, and myeloproliferative disease. CASE PRESENTATION: A 68-year-old Asian male with JAK2 V617F mutation developed four different hematologic and non-hematologic neoplastic processes. In 2009, he was diagnosed with stage IA lung adenocarcinoma and also noted to have worsening leukocytosis and thrombocytosis with peak platelet count of 1,054,000/mL)...
2016: Biomarker Research
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
Anita F Oliveira, Aline Tansini, Daniel O Vidal, Luiz F Lopes, Konradin Metze, Irene Lorand-Metze
BACKGROUND: Immunophenotyping of bone marrow (BM) hemopoietic precursors is useful for diagnosis of adult myelodysplastic syndrome (MDS), but data concerning pediatric patients are limited. We analyzed immunophenotypic features of BM cells at diagnosis of children who were referred to the Brazilian Pediatric Cooperative Group of Myelodysplastic Syndromes. METHODS: Diagnosis was based on clinical information, peripheral blood counts, BM cytology and cytogenetics...
October 17, 2016: Pediatric Blood & Cancer
Mohammad Faizan Zahid, Terra L Lasho, Christy Finke, Rhett P Ketterling, Naseema Gangat, Curtis A Hanson, Ayalew Tefferi, Mrinal M Patnaik
No abstract text is available yet for this article.
October 14, 2016: Leukemia & Lymphoma
Mrinal M Patnaik, Daniela Barraco, Terra L Lasho, Christy M Finke, Curtis A Hanson, Rhett P Ketterling, Naseema Gangat, Ayalew Tefferi
DNMT3A mutations are seen in ∼5% of patients with chronic myelomonocytic leukemia (CMML) and thus far, have had an indeterminate prognostic impact on survival. We carried out this study to assess the prognostic impact of DNMT3A mutations on a larger informative cohort of CMML patients (n=261). DNMT3A mutations were seen in 6% (n=16); 56% (n=9) male, with a median age of 64 years. Eighty-one % of DNMT3A mutations were missense, with the Arg882 mutational hot spot accounting for 63% of all changes. Five (31%) patients had an abnormal karyotype whereas concurrent gene mutations (SF3B1/SRSF2/U2AF1-56%, TET2-50%, and ASXL1-25%) were seen in all patients...
October 12, 2016: American Journal of Hematology
Michele N Edison, M Cody O'Dell, Haley P Letter, Kurt Scherer, Jennifer L Williams
An 8-year-old girl presented with bilateral breast masses and was subsequently diagnosed with juvenile myelomonocytic leukemia. Juvenile myelomonocytic leukemia is a rare myelodysplastic syndrome that typically presents in boys younger than 3 years of age with splenomegaly, lymphadenopathy and skin findings. Bilateral breast masses in a child are rare and, as such, present a diagnostic dilemma due to the relative paucity of cases in the literature. We present a case of granulocytic sarcoma of the breasts in a patient with juvenile myelomonocytic leukemia...
October 7, 2016: Pediatric Radiology
Markus Ball, Alan F List, Eric Padron
Exome sequencing studies in Chronic Myelomonocytic Leukemia (CMML) illustrate a mutational landscape characterized by few somatic mutations involving a subset of recurrent gene mutations in ASXL1, SRSF2, and TET2, each approaching 40% in incidence. This has led to the clinical implementation of next generation sequencing panels that effectively identify clonal monocytosis and complement clinical prognostic scoring systems in most patients. However, most murine models based on single gene mutations fail to recapitulate the CMML phenotype and many gene mutations are loss-of-function making the identification of traditional therapeutic vulnerabilities challenging...
October 5, 2016: Blood
John M Bennett
In comparison with the 2008 World Health Organization "Blue Book" on hematopoietic neoplasms, a small number of changes have been made in the classification. In the lower-risk patients, Refractory Cytopenias with Multilineage Dysplasia and Ring Sideroblasts (RCMD-RS) has been separated from RCMD to recognize the importance of the SF3B1 mutation. Often there has been confusion as to the degree of morphologic dysplasia and/or cytopenias to define some of the lower-risk subtypes. In addition, the type of dysplasia or cytopenias is not always concordant...
August 12, 2016: Clinical Lymphoma, Myeloma & Leukemia
Prashant Sharma, Shivani S Shinde, Moussab Damlaj, Mehrdad Hefazi Rorghabeh, Shahrukh K Hashmi, Mark R Litzow, William J Hogan, Naseema Gangat, Michelle A Elliott, Aref Al-Kali, Ayalew Tefferi, Mrinal M Patnaik
MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasm) overlap syndromes are myeloid malignancies for which allogeneic hematopoietic stem cell transplant (allo-HSCT) is potentially curative. We describe transplant outcomes of 43 patients - 35 with chronic myelomonocytic leukemia, CMML (of which 17 had blast transformation, BT) and eight with MDS/MPN-unclassifiable (MDS/MPN,U). At median follow-up of 21 months, overall survival (OS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 55%, 29%, and 25% respectively in CMML without BT and 47%, 40%, and 34% respectively in CMML with BT...
August 11, 2016: Leukemia & Lymphoma
Chetasi Talati, Eric Padron
According to the recently published 2016 World Health Organization (WHO) classification of myeloid malignancies, myelodysplastic/myeloproliferative neoplasms (MDS/MPN) include atypical chronic myeloid leukemia (aCML), MDS/MPN-unclassifiable (MDS/MPN-U), chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and MDS/MPN ring sideroblasts with thrombocytosis (MDS/MPN-RS-T). MDS/MPN-RS-T was previously a provisional category known as refractory anemia with ring sideroblasts with thrombocytosis (RARS-T) which has now attained a distinct designation in the 2016 WHO classification...
September 24, 2016: Current Hematologic Malignancy Reports
M M Patnaik, M F Zahid, T L Lasho, C Finke, R L Ketterling, N Gangat, K D Robertson, C A Hanson, A Tefferi
No abstract text is available yet for this article.
2016: Blood Cancer Journal
Masao Hagihara, Morihiro Inoue, Kenichiro Kodama, Tomoyuki Uchida, Jian Hua
An 80-year-old man was admitted to our hospital because of severe thrombocytopenia. He was diagnosed with idiopathic thrombocytopenia, and prednisolone together with eltrombopag was started, leading to significant improvement of platelet counts. Four years later, there was a prominent increase of peripheral blood monocytes, which was accompanied by recurrence of thrombocytopenia. Bone marrow aspirates and serum electrophoresis revealed coexistence of chronic myelomonocytic leukemia (CMML) and multiple myeloma (MM)...
2016: Case Reports in Hematology
K Geissler, E Jäger, A Barna, T Alendar, E Ljubuncic, T Sliwa, P Valent
No abstract text is available yet for this article.
September 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Jack W Singer, Suliman Al-Fayoumi, Haiching Ma, Rami S Komrokji, Ruben Mesa, Srdan Verstovsek
Pacritinib, potent inhibitor of Janus kinase 2 (JAK2), JAK2V617F, and fms-like receptor tyrosine kinase 3, is in Phase III development in myelofibrosis. Among type 1 inhibitors, pacritinib shows a lack of myelosuppression at doses that both inhibit JAK2/signal transducer and activator of transcription 3 pathway and demonstrate clinical efficacy. To elucidate these mechanisms and identify other disease targets, a kinome analysis screened 439 recombinant kinases at 100 nM pacritinib concentration. For kinases with >50% inhibition, pacritinib was titrated from 1 to 100 nM...
2016: Journal of Experimental Pharmacology
Radoslav Mladenov, Dmitrij Hristodorov, Christian Cremer, Gerrit Gresch, Elena Grieger, Lea Schenke, Diana Klose, Manal Amoury, Mira Woitok, Edgar Jost, Tim H Brümmendorf, Rolf Fendel, Rainer Fischer, Christoph Stein, Theo Thepen, Stefan Barth
Fc gamma receptor I (FcγRI, CD64) is a well-known target antigen for passive immunotherapy against acute myeloid leukemia and chronic myelomonocytic leukemia. We recently reported the preclinical immunotherapeutic potential of microtubule associated protein tau (MAP) against a variety of cancer types including breast carcinoma and Hodgkin's lymphoma. Here we demonstrate that the CD64-directed human cytolytic fusion protein H22(scFv)-MAP kills ex vivo 15-50% of CD64+ leukemic blasts derived from seven myeloid leukemia patients...
August 24, 2016: Oncotarget
Keith W Pratz, Michelle A Rudek, Ivana Gojo, Mark R Litzow, Michael A McDevitt, Jiuping Jay Ji, Larry Karnitz, James G Herman, Robert Kinders, B Douglas Smith, Steven D Gore, Hetty Carraway, Margaret M Showel, Douglas E Gladstone, Mark J Levis, Hua-Ling Tsai, Gary L Rosner, Alice Chen, Scott H Kaufmann, Judith Karp
PURPOSE: The poly(ADP-ribose) polymerase (PARP) inhibitor veliparib delays DNA repair and potentiates cytotoxicity of multiple classes of chemotherapy drugs, including topoisomerase I inhibitors and platinating agents. This study evaluated veliparib incorporation into leukemia induction therapy using a previously described topotecan/carboplatin backbone. EXPERIMENTAL DESIGN: Employing a 3+3 trial design, we administered escalating doses of veliparib combined with topotecan + carboplatin in relapsed or refractory acute leukemias, aggressive myeloproliferative neoplasms (MPNs) and chronic myelomonocytic leukemia (CMML)...
August 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ali N Chamseddine, Monica Cabrero, Yue Wei, Irene Ganan-Gomez, Simona Colla, Koichi Takahashi, Hui Yang, Zachary S Bohannan, Guillermo Garcia-Manero
BACKGROUND (OR PURPOSE): Inflammation has an essential role in the pathogenesis of myelodysplastic syndromes (MDS). Its expression is controlled by phosphodiesterase 4 (PDE4). Thus, PDE4 inhibitors might be useful therapeutic targets for MDS. PATIENTS (OR MATERIALS) AND METHODS: We evaluated the expression of each isoform of PDE4 (A, B, C, and D) using transcriptomic profiling and examined the potential impact on the outcome of patients with MDS in terms of survival and response to hypomethylating agents...
August 2016: Clinical Lymphoma, Myeloma & Leukemia
Hanadi Ramadan, Vu H Duong, Najla Al Ali, Eric Padron, Ling Zhang, Jeffrey E Lancet, Alan F List, Rami S Komrokji
INTRODUCTION: Eltrombopag used for thrombocytopenia in myelodysplastic syndrome (MDS) patients is being explored in clinical trials including those with chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS: We report our experience treating patients with CMML enrolled in a sequential 2-stage dose escalation study with eltrombopag in patients with MDS after hypomethylating agent failure. Patients with CMML were compared with patients with MDS in respect to response and adverse events...
August 2016: Clinical Lymphoma, Myeloma & Leukemia
Anne Boyd, Jesse Newman, Lucie Turcotte, Ingrid C Polcari
No abstract text is available yet for this article.
October 2016: Journal of Pediatrics
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