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https://www.readbyqxmd.com/read/29757120/prognostic-significance-of-srsf2-mutations-in-myelodysplastic-syndromes-and-chronic-myelomonocytic-leukemia-a-meta-analysis
#1
Pourya Arbab Jafari, Hossein Ayatollahi, Ramin Sadeghi, Maryam Sheikhi, Amir Asghari
OBJECTIVE: Serine/arginine-rich splicing factor 2 (SRSF2) mutations were detected frequently in myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) patients. However, its prognostic value has not yet been fully clarified. METHODS: In this meta-analysis, Hazard Ratio (HR) and 95% confidence interval (CI) for overall-survival (OS) were chosen to evaluate the prognostic impact of SRSF2 mutations and to compare SRSF2 mutations to those with wild-type...
May 14, 2018: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29731877/outcome-of-patient-with-high-risk-chronic-myelomonocytic-leukemia-treated-with-decitabine-prior-to-transformation-to-acute-myeloid-leukemia-a-case-report
#2
Huan Liu, Juan Cheng, Long Zhao, Qian Xu, Mingming Xue, Shuling Zhang, Bei Liu
The present study describes a patient with high-risk chronic myelomonocytic leukemia (CMML), for whom decitabine therapy achieved partial remission, prior to a sudden transformation to acute myeloid leukemia (AML) and an inferior outcome. The 53-year-old male reported easily bruising for 5 months. Examination indicated a diagnosis of CMML. Chromosome analysis identified a 48, XY, +8, +21 karyotype, classifying the patient as high-risk, according to a clinical/molecular CPSS (CPSS-Mol) model. Gene sequencing detected a mutation in DNA methyltransferase 3α, which is relatively rarely identified in CMML and has recently been reported to have an independent prognostic impact on overall survival time...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29728305/prognostic-role-of-gene-mutations-in-chronic-myelomonocytic-leukemia-patients-treated-with-hypomethylating-agents
#3
Matthieu Duchmann, Fevzi F Yalniz, Alessandro Sanna, David Sallman, Catherine C Coombs, Aline Renneville, Olivier Kosmider, Thorsten Braun, Uwe Platzbecker, Lise Willems, Lionel Adès, Michaela Fontenay, Raajit Rampal, Eric Padron, Nathalie Droin, Claude Preudhomme, Valeria Santini, Mrinal M Patnaik, Pierre Fenaux, Eric Solary, Raphael Itzykson
Somatic mutations contribute to the heterogeneous prognosis of chronic myelomonocytic leukemia (CMML). Hypomethylating agents (HMAs) are active in CMML, but analyses of small series failed to identify mutations predicting response or survival. We analyzed a retrospective multi-center cohort of 174 CMML patients treated with a median of 7 cycles of azacitidine (n = 68) or decitabine (n = 106). Sequencing data before treatment initiation were available for all patients, from Sanger (n = 68) or next generation (n = 106) sequencing...
April 25, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29712989/a-comparison-of-clinical-and-molecular-characteristics-of-patients-with-systemic-mastocytosis-with-chronic-myelomonocytic-leukemia-to-cmml-alone
#4
Mrinal M Patnaik, Rangit Vallapureddy, Terra L Lasho, Katherine P Hoversten, Christy M Finke, Rhett P Ketterling, Curtis A Hanson, Naseema Gangat, Ayalew Tefferi, Animesh Pardanani
No abstract text is available yet for this article.
April 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29707521/evaluation-by-flow-cytometry-of-mature-monocyte-subpopulations-for-the-diagnosis-and-follow-up-of-chronic-myelomonocytic-leukemia
#5
Tiphanie Picot, Carmen Mariana Aanei, Pascale Flandrin Gresta, Pauline Noyel, Sylvie Tondeur, Emmanuelle Tavernier Tardy, Denis Guyotat, Lydia Campos Catafal
Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm, characterized by persistent monocytosis and dysplasia in at least one myeloid cell lineage. This persistent monocytosis should be distinguished from the reactive monocytosis which is sometimes observed in a context of infections or solid tumors. In 2015, Selimoglu-Buet et al. observed an increased percentage of classical monocytes (CD14+ /CD16- >94%) in the peripheral blood (PB) of CMML patients. In this study, using multiparametric flow cytometry (MFC), we assessed the monocytic distribution in PB samples and in bone marrow aspirates from 63 patients with monocytosis or CMML suspicion, and in seven follow-up blood samples from CMML patients treated with hypomethylating agents (HMA)...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29666007/mutation-analysis-of-therapy-related-myeloid-neoplasms
#6
Takahiro Nishiyama, Yuichi Ishikawa, Naomi Kawashima, Akimi Akashi, Yoshiya Adachi, Hikaru Hattori, Yoko Ushijima, Hitoshi Kiyoi
We analyzed the genetic mutation status of 13 patients with therapy-related myeloid neoplasms (t-MN). Consistent with previous reports, t-MN cells preferentially acquired mutations in TP53 and epigenetic modifying genes, instead of mutations in tyrosine kinase and spliceosome genes. Furthermore, we compared the mutation status of three t-MN cells with each of the initial lymphoid malignant cells, and identified common mutations among t-MN and the initial malignant cells in two patients. In a patient who developed chronic myelomonocytic leukemia (CMML) after follicular lymphoma (FL), TET2 mutation was identified in both CMML and FL cells...
April 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29658352/chronic-subdural-collection-overlying-an-intra-axial-hemorrhagic-lesion-in-chronic-myelomonocytic-leukemia-special-report-and-review-of-the-literature
#7
Anne-Laure Bernat, Stefano Maria Priola, Ahmad Elsawy, Faisal Farrash, Shervin Taslimi, Fred Gentili
Chronic myelomonocytic leukaemia (CMML) is a clonal hematopoietic stem cell disorder characterized by the presence of an absolute monocytosis in the peripheral blood (>1 x 109 /L) and the presence of myelodysplastic and myeloproliferative features in the bone marrow. Involvement of the central nervous system (CNS) is uncommon in CMML. Areas covered: Herein described is a case report of a CMML patient who presents with symptomatic chronic subdural collection overlying a haemorrhagic brain lesion, along with diffuse dural infiltration, after two cycles of azacytidine...
April 19, 2018: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/29607228/chronic-myelomonocytic-leukemia-following-multicentric-castleman-disease
#8
Feng Li, Xiaomei Zhang, Yanting Guo, Yuandong Zhu, Yicun Wu, Yun Ling
Multicentric Castleman disease (MCD) is a rare nonmalignant lymphoproliferative disorder presenting systemic symptoms such as fever, night sweats, fatigue, anemia, effusions, and multifocal lymphadenopathy. The etiology of MCD has not been clarified to date. The coexistence of MCD with chronic myelomonocytic leukemia (CMML) has been rarely reported. Although the pathogenesis remains unclear, this association probably reflects an incidental and fortuitous finding rather than the alteration of a common pluripotent stem cell precursor...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29600428/cbl-mutation-and-mefv-single-nucleotide-variant-are-important-genetic-predictors-of-tumor-reduction-in-glucocorticoid-treated-patients-with-chronic-myelomonocytic-leukemia
#9
Junichi Watanabe, Ken Sato, Yukiko Osawa, Toshikatsu Horiuchi, Shoichiro Kato, Reina Hikota-Saga, Takaaki Maekawa, Takeshi Yamamura, Ayako Kobayashi, Shinichi Kobayashi, Fumihiko Kimura
Glucocorticoid (GC) therapy occasionally relieves tumor-related fever and promotes tumor reduction in patients with chronic myelomonocytic leukemia (CMML). A mutation analysis of 24 patients with CMML revealed the relationship of GC effectiveness, defined as a monocyte reduction of > 50% within 3 days of methylprednisolone administration, with the MEFV single-nucleotide variant (SNV) and CBL mutation. Lipopolysaccharide-stimulated monocytes harboring MEFV E148Q produced greater amounts of IL-1β and TNF-α than did wild-type monocytes; this was effectively suppressed by GC...
March 29, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29596070/chronic-myelomonocytic-leukemia-with-fibrosis-is-a-distinct-disease-subset-with-myeloproliferative-features-and-frequent-jak2-p-v617f-mutations
#10
Gur Deniz, Sanam Loghavi, Guillermo Garcia-Manero, Mark Routbort, Rashmi Kanagal-Shamanna, Andres Quesada, Haitham Khogeer, Sherry Pierce, L Jeffrey Medeiros, Hagop Kantarjian, Joseph D Khoury
A subset of patients with chronic myelomonocytic leukemia (CMML) presents with significance myelofibrosis. In myelodysplastic syndromes, significant myelofibrosis has been associated with adverse outcomes and p53 dysregulation. However, in CMML the clinical and molecular correlates of significant myelofibrosis at presentation remain poorly understood. From a cohort of 651 CMML patients, we identified retrospectively 20 (3.1%) cases with moderate to severe reticulin fibrosis (CMML-F) detected at diagnosis, and we compared them to CMML patients without fibrosis (n=631) seen during the same period...
March 28, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29572561/autoimmune-disorders-are-common-in-myelodysplastic-syndrome-patients-and-confer-an-adverse-impact-on-outcomes
#11
Julia Montoro, Laura Gallur, Brayan Merchán, Antonieta Molero, Elisa Roldán, Ferrán Martínez-Valle, Guillermo Villacampa, Mayda Navarrete, Margarita Ortega, Josep Castellví, Silvia Saumell, Sabela Bobillo, Francesc Bosch, David Valcárcel
The coexistence of autoimmune disorders (AD) in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) has been widely recognized, although with distinct results regarding their prevalence and impact on the outcomes of the underlying hematological process. This study was aimed to analyze the prevalence, clinical characteristics, and outcomes of MDS with AD in a series of 142 patients diagnosed with MDS and CMML. AD was ascertained by both the presence of clinical symptoms or compatible serological tests...
March 23, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29557496/association-of-bone-marrow-fibrosis-with-inferior-survival-outcomes-in-chronic-myelomonocytic-leukemia
#12
Maliha Khan, Tariq Muzzafar, Hagop Kantarjian, Ifra Badar, Nicholas Short, Xuemei Wang, Kamal Chamoun, Preetesh Jain, Courtney DiNardo, Naveen Pemmaraju, Prithviraj Bose, Gautam Borthakur, Jorge Cortes, Srdan Verstovsek, Guillermo Garcia-Manero, Zeev Estrov
The impact of bone marrow fibrosis grade on the prognosis of patients with chronic myelomonocytic leukemia (CMML) remains controversial. Therefore, we examined the records of 82 patients diagnosed with CMML at our institution and summarized baseline characteristics and molecular profiles by subgroups of absent or mild (grades 0/1) and moderate (grade 2) fibrosis. Cox proportional hazards models were constructed to assess the prognostic significance of fibrosis grade. Grade 2 fibrosis was identified in 63 patients (76...
March 20, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29479066/utx-loss-causes-myeloid-transformation
#13
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
https://www.readbyqxmd.com/read/29475821/systematic-literature-review-of-treatment-options-and-clinical-outcomes-for-patients-with-higher-risk-myelodysplastic-syndromes-and-chronic-myelomonocytic-leukemia
#14
REVIEW
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...
April 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29423961/pruritic-arthropod-bite-like-papules-in-t-cell-large-granular-lymphocytic-leukaemia-and-chronic-myelomonocytic-leukaemia
#15
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
https://www.readbyqxmd.com/read/29384408/octasomy-21-in-a-patient-with-secondary-aml-after-cmml-the-role-of-acquired-nras-mutations-in-triggering-aneuploidy
#16
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
https://www.readbyqxmd.com/read/29310473/a-new-approach-for-diagnosing-chronic-myelomonocytic-leukemia-using-structural-parameters-of-sysmex-xn-tm-analyzers-in-routine-laboratory-practice
#17
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...
May 2018: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/29296739/engraftment-of-chronic-myelomonocytic-leukemia-cells-in-immunocompromised-mice-supports-disease-dependency-on-cytokines
#18
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
https://www.readbyqxmd.com/read/29288910/3q26-evi1-rearrangement-in-myelodysplastic-myeloproliferative-neoplasms-an-early-event-associated-with-a-poor-prognosis
#19
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...
February 2018: Leukemia Research
https://www.readbyqxmd.com/read/29275866/cooperative-epigenetic-remodeling-by-tet2-loss-and-nras-mutation-drives-myeloid-transformation-and-mek-inhibitor-sensitivity
#20
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...
January 8, 2018: Cancer Cell
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