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Myeloid leukemia

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https://www.readbyqxmd.com/read/28350881/correction-gata2-inhibition-sensitizes-acute-myeloid-leukemia-cells-to-chemotherapy
#1
Li Yang, Hanxiao Sun, Yanan Cao, Binbin Xuan, Yingchao Fan, Huiming Sheng, Wenfang Zhuang
[This corrects the article DOI: 10.1371/journal.pone.0170630.].
2017: PloS One
https://www.readbyqxmd.com/read/28350519/outcome-of-lower-risk-patients-with-myelodysplastic-syndromes-without-5q-deletion-after-failure-of-erythropoiesis-stimulating-agents
#2
Sophie Park, Jean-François Hamel, Andrea Toma, Charikleia Kelaidi, Sylvain Thépot, Maria Diez Campelo, Valeria Santini, Mikkael A Sekeres, Enrico Balleari, Jennifer Kaivers, Rosa Sapena, Katharina Götze, Catharina Müller-Thomas, Odile Beyne-Rauzy, Aspasia Stamatoullas, Ioannis Kotsianidis, Rami Komrokji, David P Steensma, Jaime Fensterl, Gail J Roboz, Teresa Bernal, Fernando Ramos, Marisa Calabuig, Agnès Guerci-Bresler, Dominique Bordessoule, Pascale Cony-Makhoul, Stéphane Cheze, Eric Wattel, Christian Rose, Norbert Vey, Daniela Gioia, Dario Ferrero, Gianluca Gaidano, Giovanni Cametti, Fabrizio Pane, Alessandro Sanna, Ulrich Germing, Guillermo F Sanz, François Dreyfus, Pierre Fenaux
Purpose Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Second-line treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments...
March 28, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28345823/mutation-analysis-of-isocitrate-dehydrogenase-idh1-2-and-dna-methyltransferase-3a-dnmt3a-in-thai-patients-with-newly-diagnosed-acute-myeloid-leukemia
#3
Tanasan Sirirat, Suporn Chuncharunee, Pimjai Nipaluk, Teerapong Siriboonpiputtana, Takol Chareonsirisuthigul, Nittaya Limsuwannachot, Budsaba Rerkamnuaychoke
Acute myeloid leukemia (AML) is a clonal hematopoietic stem/progenitor cell disorder which features several genetic mutations. Recurrent genetic alterations identified in AML are recognized as causes of the disease, finding application as diagnostic, prognostic and monitoring markers, with potential use as targets for cancer therapy. Here, we performed a pyrosequencing technique to investigate common mutations of IDH1, IDH2 and DNMT3A in 81 newly diagnosed AML patients. The prevalences of IDH1, IDH2 and DNMT3A mutations were 6...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28345491/a-comparison-of-toxicities-in-acute-myeloid-leukemia-patients-with-and-without-renal-impairment-treated-with-decitabine
#4
Lauren B Levine, Julianna Vf Roddy, Miryoung Kim, Junan Li, Gary Phillips, Alison R Walker
Purpose There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater. Methods We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min)...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28344320/dpp4-truncated-gm-csf-il-3-manifest-distinct-receptor-binding-regulatory-functions-compared-to-their-full-length-forms
#5
H A O'Leary, M Capitano, S Cooper, C Mantel, H S Boswell, R Kapur, B Ramdas, R Chan, L Deng, C-K Qu, H E Broxmeyer
Dipeptidylpeptidase 4 (DPP4/CD26) enzymatically cleaves select penultimate amino acids of proteins, including colony stimulating factors (CSFs), and has been implicated in cellular regulation. To better understand the role of DPP4 regulation of hematopoiesis, we analyzed the activity of DPP4 on the surface of immature blood cells and then comparatively assessed the interactions and functional effects of full-length (FL) and DPP4 truncated factors [(T)-GM-CSF and- IL-3] on both in vitro and in vivo models of normal and leukemic cells...
March 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28343875/discovery-and-structure-activity-relationship-studies-of-n-substituted-indole-derivatives-as-novel-mcl-1-inhibitors
#6
Shenglin Luan, Qi Ge, Yedong Chen, Mingyang Dai, Jinyu Yang, Kun Li, Dan Liu, Linxiang Zhao
Myeloid cell leukemia-1 (Mcl-1) is an important antiapoptotic protein functioning through protein-protein interactions. We discovered LSL-A6 (2-((2-carbamoyl-1-(3-(4-methoxyphenoxy)propyl)-1H-indol-6-yl)oxy)acetic acid) with a novel N-substituted indole scaffold to interfere Mcl-1 binding as a novel Mcl-1 inhibitor. Molecular modeling indicated that this compound binds with Mcl-1 by interaction with P2 and R263 hot-spots. Structure modification focused on several moieties including indole core, hydrophobic tail and acidic chain were conducted and structure-activity relationship was analyzed...
March 16, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28342811/myeloid-sarcoma-presentation-diagnosis-and-treatment
#7
REVIEW
L Max Almond, Maria Charalampakis, Samuel J Ford, David Gourevitch, Anant Desai
Myeloid sarcoma is an extramedullary tumor of immature granulocytic cells. It is a rare condition, most often associated with acute myeloid leukemia (AML), although in some rare cases it may present in nonleukemic patients. It should therefore be considered as a differential diagnosis of any atypical cellular infiltrate. It may occur at any site, leading to very varied clinical presentations. Diagnosis is challenging and relies on a high index of suspicion as well as radiology, histology, immunophenotyping, and molecular analyses, which also are essential for risk stratification and treatment planning...
March 7, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28342808/role-of-mtorc1-s6k1-signaling-pathway-in-regulation-of-hematopoietic-stem-cell-and-acute-myeloid-leukemia
#8
REVIEW
Joydeep Ghosh, Reuben Kapur
Dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1)-p70 ribosomal protein kinase 1 (S6K1) signaling pathway occurs frequently in acute myeloid leukemia (AML) patients. This pathway also plays a critical role in maintaining normal cellular processes. Given the importance of leukemia stem cells (LSC) in the development of minimal residual disease (MRD), it is critical to use therapeutic interventions that target LSC population to prevent disease relapse. mTORC1-S6K1 pathway has been identified as an important regulator of hematopoietic stem cell (HSC) and LSC functions...
March 22, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28341918/dasatinib-versus-imatinib-in-japanese-patients-with-newly-diagnosed-chronic-phase-chronic-myeloid-leukemia-a-subanalysis-of-the-dasision-5-year-final-report
#9
Hirohisa Nakamae, Shin Fujisawa, Michinori Ogura, Toshiki Uchida, Yasushi Onishi, Masafumi Taniwaki, Atae Utsunomiya, Kosei Matsue, Yasushi Takamatsu, Kensuke Usuki, Mitsune Tanimoto, Yoji Ishida, Kazuteru Ohashi, Li Li, Masafumi Miyoshi
The international phase III DASISION trial demonstrated improved efficacy of dasatinib versus imatinib in treatment-naive patients with chronic myeloid leukemia in the chronic phase (CML-CP). We report efficacy and safety outcomes in a Japanese population from the final, 5-year follow-up of DASISION. At the end of the study, 77% (20/26) of dasatinib-treated and 61% (14/23) of imatinib-treated patients remained on initial therapy. Improved responses were observed in Japanese patients who received dasatinib versus imatinib (complete cytogenetic response: 96 vs 87%; major molecular response: 88 vs 74%; BCR-ABL1 ≤0...
March 24, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28341738/higher-hopx-expression-is-associated-with-distinct-clinical-and-biological-features-and-predicts-poor-prognosis-in-de-novo-acute-myeloid-leukemia
#10
Chien-Chin Lin, Yueh-Chwen Hsu, Yi-Hung Li, Yuan-Yeh Kuo, Hsin-An Hou, Keng-Hsueh Lan, Tsung-Chih Chen, Yi-Shiuan Tzeng, Yi-Yi Kuo, Chein-Jun Kao, Po-Han Chuang, Mei-Hsuan Tseng, Yu-Chiao Chiu, Wen-Chien Chou, Hwei-Fang Tien
Homeodomain-only protein homeobox (HOPX) is the smallest homeodomain protein. It was regarded as a stem cell marker in several non-hematopoietic systems. While the prototypic homeobox genes such as HOX family have been well characterized in acute myeloid leukemia, the clinical and biological implications of HOPX in the disease remain unknown. Thus we analyzed HOPX and global gene expression patterns in 347 newly diagnosed de novo acute myeloid leukemia patients in our institute. We found that higher HOPX expression was closely associated with older age, higher platelet counts, lower white blood cell counts, lower lactate dehydrogenase levels, and mutations in RUNX1, IDH2, ASXL1, and DNMT3A, but negatively associated with acute promyelocytic leukemia, favorable karyotypes, CEBPA double mutations and NPM1 mutation...
March 24, 2017: Haematologica
https://www.readbyqxmd.com/read/28341737/abnormal-bone-marrow-microenvironment-contributes-to-hematopoietic-dysfunction-in-fanconi-anemia
#11
Yuan Zhou, Yongzheng He, Wen Xing, Peng Zhang, Hui Shi, Shi Chen, Jun Shi, Jie Bai, Steven D Rhodes, Fengkui Zhang, Jin Yuan, Xianlin Yang, Xiaofan Zhu, Yan Li, Helmut Hanenberg, Mingjiang Xu, Kent A Robertson, Weiping Yuan, Grzegorz Nalepa, Tao Cheng, D Wade Clapp, Feng-Chun Yang
Fanconi anemia is a complex heterogeneous genetic disorder with a high incidence of bone marrow failure, clonal evolution to acute myeloid leukemia and mesenchymal-derived congenital anomalies. Increasing evidence in Fanconi anemia and other genetic disorders points towards an interdependence of skeletal and hematopoietic development, yet the impact of the marrow microenvironment in the pathogenesis of the bone marrow failure in Fanconi anemia remains unclear. Here we demonstrated that mice with double knockout of both Fancc and Fancg gene had decreased bone formation at least partially due to impaired osteoblast differentiation from mesenchymal stem/progenitor cells...
March 24, 2017: Haematologica
https://www.readbyqxmd.com/read/28341518/evaluation-of-the-implementation-rate-of-primary-antifungal-prophylaxis-and-the-prognosis-of-invasive-fungal-disease-in-acute-leukemia-patients-in-china
#12
Xiao-Han Xu, Lu Zhang, Xin-Xin Cao, Jian Li, Wei Zhang, Tie-Nan Zhu, Hua-Cong Cai, Miao Chen, Xiao Han, Chen Yang, Bing Han, Yan Zhang, Jun-Ling Zhuang, Dao-Bin Zhou, Ming-Hui Duan
BACKGROUND: Invasive fungal disease (IFD) is a major complication of acute leukemia, thus primary antifungal prophylaxis (PAP) is recommended by guidelines. Nevertheless, guidelines might not be commonly followed in developing countries due to economic factors. The primary objectives were to evaluate the implementation rate of PAP in acute leukemia patients in China and to compare the prognosis of IFD with and without PAP. The secondary objectives were to investigate the safety of PAP, clinical characteristics of IFDs and risk factors of breakthrough...
March 21, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28340577/gene-and-protein-analysis-reveals-that-p53-pathway-is-functionally-inactivated-in-cytogenetically-normal-acute-myeloid-leukemia-and-acute-promyelocytic-leukemia
#13
Julia Abramowitz, Tzahi Neuman, Riki Perlman, Dina Ben-Yehuda
BACKGROUND: Mechanisms that inactivate the p53 pathway in Acute Myeloid Leukemia (AML), other than rare mutations, are still not well understood. METHODS: We performed a bioinformatics study of the p53 pathway function at the gene expression level on our collection of 1153 p53-pathway related genes. Publically available Affymetrix data of 607 de-novo AML patients at diagnosis were analyzed according to the patients cytogenetic, FAB and molecular mutations subtypes...
March 24, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28340210/clinical-significance-of-isolated-myeloperoxidase-expression-in-pediatric-b-lymphoblastic-leukemia
#14
Matthew J Oberley, Sisi Li, Etan Orgel, Choo Phei Wee, Ashley Hagiya, Maurice R G O'Gorman
Objectives: Diagnosis of B-cell acute lymphoblastic leukemia (B-ALL) requires immunophenotypic evidence of B-lineage and absence of specific myeloid or T-lineage markers. Rare cases of otherwise typical B-ALL express myeloperoxidase (MPO) detectable by flow cytometry with an absence of other myeloid markers, but the clinical significance of this finding is not well studied. Methods: A retrospective cohort analysis of flow cytometry and clinical data was performed to investigate the clinical outcome of this specific group of patients...
March 15, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28340113/gata1-is-a-sensitive-and-specific-nuclear-marker-for-erythroid-and-megakaryocytic-lineages
#15
Winston Y Lee, Olga K Weinberg, Geraldine S Pinkus
Objectives: GATA binding factor 1 (GATA1) is a transcription factor essential for erythromegakaryocytic differentiation. Given its function in lineage specification, we sought to evaluate the immunohistochemical profile of GATA1 in normal marrow and acute leukemia and assess the use of GATA1 as a specific erythromegakaryocytic immunohistochemical marker. Methods: Immunohistochemical studies for GATA1 expression were performed on bone marrow biopsy specimens to define its role in the evaluation of acute leukemia and other hematologic disorders...
March 15, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28339029/hydroxychloroquine-sensitizes-chronic-myeloid-leukemia-cells-to-v%C3%AE-9v%C3%AE-2-t-cell-mediated-lysis-independent-of-autophagy
#16
Biqing Han, Yanmin Zhao, Yu Lin, Shan Fu, Limengmeng Wang, Mingming Zhang, Ruxiu Tie, Binsheng Wang, Yi Luo, Lizhen Liu, Jian Yu, He Huang
Hydroxychloroquine (HCQ) is the only autophagy inhibitor in clinical use and it has shown great potential in treating chronic myeloid leukemia (CML). By inhibiting autophagy, HCQ enhances the anti-CML efficiency of chemotherapy. In the present study, we demonstrated that HCQ sensitized CML cells to Vγ9Vδ2 T cell-mediated lysis. HCQ inhibited autophagy in CML cells, but the sensitizing effects of HCQ were autophagy-independent. Since the sensitization was not mimicked by ATG7 knockdown and even occurred in the absence of ATG7...
March 24, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28338652/3q26-2-evi1-rearrangement-is-associated-with-poor-prognosis-in-classical-philadelphia-chromosome-negative-myeloproliferative-neoplasms
#17
Zhihong Hu, L Jeffrey Medeiros, Wei Wang, Zi Chen, Guilin Tang, Parsa Hodjat, Su Yang, Lianghua Fang, Yan Li, Srdan Verstovsek, Shimin Hu
Classical Philadelphia chromosome-negative myeloproliferative neoplasms are a group of closely related myeloid disorders with different histologic features and clinical presentations at an early stage, but all later develop into a similar fibrotic stage with variable risk of acute transformation. The significance of 3q26.2/EVI1 rearrangement has been well recognized in acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia. However, the clinical importance of 3q26.2/EVI1 rearrangement in classical Philadelphia chromosome-negative myeloproliferative neoplasms is unknown...
March 24, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28338290/identification-of-natural-inhibitors-of-bcr-abl-for-the-treatment-of-chronic-myeloid-leukemia
#18
Phani Krishna, Sailu Sarvagalla, Bindu Madhuri, Sankar Pajaniradje, Vinitha Baskaran, Mohane Selvaraj Coumar, R Baskaran
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of the hematopoietic stem cells, characterized at the molecular level by the bcr/abl gene rearrangement. Even though targeting the fusion gene product Bcr-Abl protein is a successful strategy, development of drug resistance and drug intolerance are currently the limitations for Bcr-Abl targeted CML therapy. With an aim to develop natural Bcr-Abl inhibitors, we performed virtual screening (VS) of ZINC natural compound database by docking with Abl kinase using Glide software...
March 24, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28338082/a-clinical-trial-for-patients-with-acute-myeloid-leukemia-or-myelodysplastic-syndromes-not-eligible-for-standard-clinical-trials
#19
G Montalban-Bravo, X Huang, K Naqvi, E Jabbour, G Borthakur, C D DiNardo, N Pemmaraju, J Cortes, S Verstovsek, T Kadia, N Daver, W Wierda, Y Alvarado, M Konopleva, F Ravandi, Z Estrov, N Jain, A Alfonso, M Brandt, T Sneed, H C Chen, H Yang, C Bueso-Ramos, S Pierce, E Estey, Z Bohannan, H M Kantarjian, G Garcia-Manero
No abstract text is available yet for this article.
March 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28337888/decitabine-treatment-for-acute-myeloid-leukemia-relapse-after-allogeneic-hematopoietic-stem-cell-transplantation
#20
X L Liu, X Zhao, C Wang, S J Gao, Y H Tan
Therapeutic options for patients with relapse of acute myeloid leukemia (AML) after allo-SCT are limited. Here, we present a case of a 49-year female with AML who underwent myeloablative allo-SCT from a matched sibling donor. Seven months after transplantation she developed cGVHD and suffered from extramedullary plus concurrent medullary relapse. The presence of CNS extramedullary disease is unique. Our patient was treated with decetabine. After one cycle the patient achieved complete remission and full donor chimerism without severe side effects or the occurrence of GVHD...
January 2017: Journal of Biological Regulators and Homeostatic Agents
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