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Leukemia myelomonocytic chronic

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https://www.readbyqxmd.com/read/28522578/mutated-asxl1-and-number-of-somatic-mutations-as-possible-indicators-of-progression-to-chronic-myelomonocytic-leukemia-of-myelodysplastic-syndromes-with-single-or-multilineage-dysplasia
#1
Ana Valencia-Martinez, Alessandro Sanna, Erico Masala, Elisa Contini, Alice Brogi, Antonella Gozzini, Valeria Santini
No abstract text is available yet for this article.
May 18, 2017: Haematologica
https://www.readbyqxmd.com/read/28498370/validation-of-response-assessment-according-to-international-consortium-for-mds-mpn-criteria-in-chronic-myelomonocytic-leukemia-treated-with-hypomethylating-agents
#2
M Duchmann, T Braun, J-B Micol, U Platzbecker, S Park, S Pilorge, O Beyne-Rauzy, N Vey, M Sébert, B Gruson, P-Y Dumas, R Guieze, M-L Chretien, K Laribi, Y Chait, L Legros, L Sahnes, P Hirsch, C Salanoubat, E Solary, P Fenaux, R Itzykson
No abstract text is available yet for this article.
May 12, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28486043/randomized-phase-ii-study-of-azacitidine-alone-or-in-combination-with-lenalidomide-or-with-vorinostat-in-higher-risk-myelodysplastic-syndromes-and-chronic-myelomonocytic-leukemia-north-american-intergroup-study-swog-s1117
#3
Mikkael A Sekeres, Megan Othus, Alan F List, Olatoyosi Odenike, Richard M Stone, Steven D Gore, Mark R Litzow, Rena Buckstein, Min Fang, Diane Roulston, Clara D Bloomfield, Anna Moseley, Aziz Nazha, Yanming Zhang, Mario R Velasco, Rakesh Gaur, Ehab Atallah, Eyal C Attar, Elina K Cook, Alyssa H Cull, Michael J Rauh, Frederick R Appelbaum, Harry P Erba
Purpose Azacitidine is standard, first-line therapy in higher-risk myelodysplastic syndromes (MDS). Whether azacitidine-based combinations with lenalidomide or vorinostat produce superior overall response rates (ORRs) to azacitidine is not known. Patients and Methods North American Intergroup Study S1117 is a phase II/III trial that randomly assigned patients with higher-risk MDS and chronic myelomonocytic leukemia (CMML) 1:1:1 to azacitidine (75 mg/m(2)/day on days 1 to 7 of a 28-day cycle); azacitidine plus lenalidomide (10 mg/day on days 1 to 21); or azacitidine plus vorinostat (300 mg twice daily on days 3 to 9)...
May 9, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28455647/cmml-clinical-and-molecular-aspects
#4
REVIEW
Raphael Itzykson, Matthieu Duchmann, Nolwenn Lucas, Eric Solary
Chronic Myelomonocytic Leukemia is a chronic myeloid neoplasm occurring mostly in the elderly with overlapping features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) characterized by chronic monocytosis. Recent progresses in the molecular and cellular pathogenesis of CMML have stirred a renewed interest in this clinically heterogeneous disorder. Here, we review the recent progresses in the biology of CMML and how it affects its current and future clinical management.
June 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28447248/somatic-setbp1-mutations-in-myeloid-neoplasms
#5
REVIEW
Hideki Makishima
SETBP1 is a SET-binding protein regulating self-renewal potential through HOXA-protein activation. Somatic SETBP1 mutations were identified by whole exome sequencing in several phenotypes of myelodysplastic/myeloproliferative neoplasms (MDS/MPN), including atypical chronic myeloid leukemia, chronic myelomonocytic leukemia, and juvenile myelomonocytic leukemia as well as in secondary acute myeloid leukemia (sAML). Surprisingly, its recurrent somatic activated mutations are located at the identical positions of germline mutations reported in congenital Schinzel-Giedion syndrome...
June 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28442268/generalized-palisaded-neutrophilic-and-granulomatous-dermatitis-a-cutaneous-manifestation-of-chronic-myelomonocytic-leukemia-a-clinical-histopathological-and-molecular-study-of-three-cases
#6
Birgit Federmann, Irina Bonzheim, Amir S Yazdi, Janine Schmidt, Falko Fend, Gisela Metzler
Palisaded neutrophilic and granulomatous dermatitis (PNGD) is characterized by erythematous papules or plaques on trunk or limbs and is frequently associated with rheumatological, autoimmune or hematological malignancies. Histopathology shows interstitial granulomas composed of epitheloid histiocytes in the reticular dermis with surrounding foci of collagen degeneration and variable neutrophilic inflammation. We report three cases of generalized PNGD associated with chronic myelomonocytic leukemia (CMML), a myelodysplastic/myeloproliferative neoplasm, which may show a variety of cutaneous manifestations...
April 22, 2017: Human Pathology
https://www.readbyqxmd.com/read/28370365/monocytosis-in-polycythemia-vera-clinical-and-molecular-correlates
#7
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
#8
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
#9
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/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
#10
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/28359030/increase-of-dna-damage-and-alteration-of-the-dna-damage-response-in-myelodysplastic-syndromes-and-acute-myeloid-leukemias
#11
Henning D Popp, Nicole Naumann, Susanne Brendel, Thomas Henzler, Christel Weiss, Wolf-Karsten Hofmann, Alice Fabarius
Increased DNA damage and alteration of the DNA damage response (DDR) are critical features of genetic instability presumably implicated in pathogenesis of myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML). We used immunofluorescence staining of γH2AX and 53BP1 for analyzing DNA double-strand breaks (DSB) in MDS and AML cell lines, in CD34+ selected cells of normal and MDS bone marrow (including three cases of chronic myelomonocytic leukemias) and in blasts of AML bone marrow. In addition, we screened for activation of the DDR by immunoblotting of p-ATM, p-ATR, p-CHK1, p-CHK2 and p-TP53...
March 21, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28296991/clinicopathologic-immunohistochemical-and-molecular-features-of-histiocytoid-sweet-syndrome
#12
Victoria Alegría-Landa, Socorro María Rodríguez-Pinilla, Angel Santos-Briz, José Luis Rodríguez-Peralto, Victor Alegre, Lorenzo Cerroni, Heinz Kutzner, Luis Requena
Importance: Histiocytoid Sweet syndrome is a rare histopathologic variant of Sweet syndrome. The nature of the histiocytoid infiltrate has generated considerable controversy in the literature. Objective: The main goal of this study was to conduct a comprehensive overview of the immunohistochemical phenotype of the infiltrate in histiocytoid Sweet syndrome. We also analyze whether this variant of Sweet syndrome is more frequently associated with hematologic malignancies than classic Sweet syndrome...
March 15, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28292946/nox2-dependent-immunosuppression-in-chronic-myelomonocytic-leukemia
#13
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/28286197/a-lot-to-learn-about-allogeneic-hematopoietic-cell-transplantation-for-chronic-myelomonocytic-leukemia
#14
Guillermo F Sanz
No abstract text is available yet for this article.
March 9, 2017: Biology of Blood and Marrow Transplantation
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
#15
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
#16
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
#17
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
#18
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 knockin mice for Cbl that express wild-type Cbl in a steady state and inducibly express Cbl(Q367P) , a CMML-associated Cbl mutant...
April 13, 2017: Blood
https://www.readbyqxmd.com/read/28205462/atypical-chronic-myeloid-leukemia-in-a-german-shepherd-dog
#19
Christina L Marino, Jimmy N S N Tran, Tracy Stokol
A 4-y-old neutered male German Shepherd Dog was presented with a 3-d duration of lethargy, restlessness, and vomiting. Physical examination revealed generalized lymphadenopathy, pale mucous membranes, systolic heart murmur, dehydration, and fever. Hematologic abnormalities included moderate-to-marked leukocytosis, characterized by neutrophilia with a left shift to progranulocytes and 2% presumptive myeloid blasts, marked anemia that was nonregenerative, and marked thrombocytopenia. Dysplasia was evident in neutrophils and platelets...
February 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28179279/role-of-runx1-in-hematological-malignancies
#20
REVIEW
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. Germ line mutations in RUNX1 cause familial platelet disorder with associated myeloid malignancies. Somatic mutations and chromosomal rearrangements involving RUNX1 are frequently observed in myelodysplastic syndrome and leukemias of myeloid and lymphoid lineages, that is, acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myelomonocytic leukemia...
April 13, 2017: Blood
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