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Acute promyelocytic leukemia

Katrin Noack, Oliver H Krämer
The differentiation of hematopoietic stem cells into mature blood cells is a highly ordered process and dysregulation of this process can lead to leukemogenesis. Agents that are used to cure acute promyelocytic leukemia (APL) can induce differentiation and/or apoptosis. Here, we describe how effects of all-trans retinoic acid (ATRA) and histone deacetylase inhibitors (HDACi) on APL cell differentiation can be evaluated by immunoblotting and by flow cytometry. We show how the levels of differentiation-associated transcription factors of the CCAAT enhancer binding protein (C/EBP) family can be determined by Western blot and we explain how the cell surface expression of the leukocyte surface antigen CD11b can be measured by flow cytometry...
2017: Methods in Molecular Biology
Michael R Loken, Andrew P Voigt, Lisa Eidenschink Brodersen, Wayne Fritschle, Andrew J Menssen, Soheil Meshinchi, Denise A Wells
Five reference populations in bone marrow specimens were identified by flow cytometry using specific combinations of reagents in order define the variation of gene product expression intensities both within and between individuals. Mature lymphocytes, uncommitted progenitor cells, promyelocytes, mature monocytes and mature neutrophils can be reproducibly identified as distinct clusters of events in heterogeneous, maturing bone marrow specimens. Support Vector Machines were used to identify the reference populations in order to reduce subjective bias in manually defining boundaries of these populations since they were not discretely separated from the remainder of the cells...
October 18, 2016: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Anliang Huang, Dan Yue, Danying Liao, Liuliu Cheng, Jinhu Ma, Yuquan Wei, Aiping Tong, Ping Cheng
Arsenic trioxide (ATO) has demonstrated clinical efficacy in acute promyelocytic leukemia (APL) and in vitro activity in various solid tumors. As2O3 as single agent exhibits poor efficacy for treatment of hepatocellular carcinoma (HCC) in phase II trial, suggesting that new modalities of treatment with enhanced therapeutic effect and alleviated toxicity are needed for application of As2O3 on patients with HCC. Survivin is the strongest inhibitor of apoptosis protein over-expressed in tumors, which has been proposed as an attractive target for new anticancer interventions...
October 11, 2016: Oncology Reports
David Gómez-Almaguer, Edson René Marcos-Ramírez, Efreen Horacio Montaño-Figueroa, Guillermo J Ruiz-Argüelles, Carlos Roberto Best-Aguilera, María Del Carmen López-Sánchez, Esperanza Barrera-Chairez, José Luis López-Arrollo, Christian Omar Ramos-Peñafiel, Andrés León-Peña, Elías Eugenio González-López, Perla Edith Rivas-García, Carlos Alberto Tellez-Hinojosa, Andrés Gómez-De León, José Carlos Jaime-Pérez
BACKGROUND: The incidence of acute leukemia (AL) has increased. Its prognosis is variable and depends on several baseline characteristics with a highly heterogeneous presentation. In Mexico, large-scale descriptive studies have not yet been published; the objective of this study was to analyze the initial basic characteristics of patients diagnosed with AL in our population. PATIENTS AND METHODS: In this multicenter, retrospective study, 1018 patients ≥ 16 years of age and diagnosed with AL between 2009 and 2014, were included...
September 17, 2016: Clinical Lymphoma, Myeloma & Leukemia
Zhen-Hua Chen, Wen-Tao Wang, Wei Huang, Ke Fang, Yu-Meng Sun, Shu-Rong Liu, Xue-Qun Luo, Yue-Qin Chen
Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are of great importance in different cell contexts. However, only a very small number of lncRNAs have been experimentally validated and functionally annotated during human hematopoiesis. Here, we report an lncRNA, HOTAIRM1, which is associated with myeloid differentiation and has pivotal roles in the degradation of oncoprotein PML-RARA and in myeloid cell differentiation by regulating autophagy pathways. We first revealed that HOTAIRM1 has different variants that are expressed at different levels in cells and that the expression pattern of HOTAIRM1 is closely related to that of the PML-RARA oncoprotein in acute promyelocytic leukemia (APL) patients...
October 14, 2016: Cell Death and Differentiation
Na Gao, Wen-Zheng Yu, Nong-Jian Guo, Xue-Xia Wang, Jian-Rong Sun
Galectin-3 plays an increasingly important role in development and progression of tumor. However, little is known about the clinical impact of galectin-3 in non-acute promyelocytic leukemia (non-M3 AML). Peripheral blood of 298 patients with primary non-M3 AML and 30 normal donors was collected for measurement of galectin-3. Galectin-3 levels were significantly higher compared with the control group (p < .001). Patients with higher galectin-3 levels had lower CR rates (p = .001) and 1-year overall survival (OS) rates (p = ...
October 13, 2016: Leukemia & Lymphoma
Sougat Misra, Arun Kumar Selvam, Marita Wallenberg, Aditya Ambati, András Matolcsy, Isabelle Magalhaes, Gilbert Lauter, Mikael Björnstedt
Selective targeting of the PML/RARα oncoprotein demonstrates a successful molecular targeted therapy in acute promyelocytic leukemia (APL) with a typical t(15:17) chromosomal translocation. The zinc-thiolate coordination is critical for structural stability of zinc finger proteins, including the PML moiety of PML/RARα. Based on the known interaction of redox-active selenium compounds with thiolate ligands of zinc, we herein have investigated the abrogatory effects of selenite alone or in combination with all-trans retinoic acid on PML/RARα and the possible effects on differentiation in these cells...
October 8, 2016: Oncotarget
Nitin Yashas Murthy, Sanjukta Rao, Delon D'souza, Abdul Matheen, Ratnamala Chaudhary
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Noriko Takahashi, Toshihiro Ohba, Masahiko Imai, Shinya Hasegawa, Katsuhiko Takahashi, Masahiro Yamasaki, Yuri Kameoka
Retinoic acid (RA) has a variety of biological effects in mammalian cells and tissues. It is well known that RA induces differentiation of human acute promyelocytic leukemia (APL) HL60 cells, fresh human APL cells, and clinical remission in patients with APL. Retinoylation (acylation of proteins by RA) is a possible pathway for RA action. However, an understanding of the role that retinoylation plays in the actions of RA is lacking. In the current study, several retinoylated proteins were detected in RA-treated HL60 fractions following Mono Q anion exchange chromatography and analysis using two-dimensional polyacrylamide gel electrophoresis...
October 6, 2016: Biochimica et Biophysica Acta
V Madan, P Shyamsunder, L Han, A Mayakonda, Y Nagata, J Sundaresan, D Kanojia, K Yoshida, S Ganesan, N Hattori, N Fulton, K T Tan, T Alpermann, M C Kuo, S Rostami, J Matthews, M Sanada, L-Z Liu, Y Shiraishi, S Miyano, E Chendamarai, H A Hou, G Malnassy, T Ma, M Garg, L W Ding, Q Y Sun, W Chien, T Ikezoe, M Lill, A Biondi, R A Larson, B L Powell, M Lübbert, W J Chng, H F Tien, M Heuser, A Ganser, M Koren-Michowitz, S M Kornblau, H M Kantarjian, D Nowak, W K Hofmann, H Yang, W Stock, A Ghavamzadeh, K Alimoghaddam, T Haferlach, S Ogawa, L Y Shih, V Mathews, H P Koeffler
No abstract text is available yet for this article.
October 7, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Junjie Huang, Min Sun, Zitong Wang, Qiaoxia Zhang, Jin Lou, Yun Cai, Weihong Chen, Xin Du
BACKGROUND: 9 treatments for acute promyelocytic leukemia (APL) have been compared in many randomized controlled trials (RCT). The conclusions have been inconsistent and the purpose of this study is to conduct a network meta-analysis. RESULTS: Rankings of event-free survival are ATRA+RIF (81.2%), ATRA+ATO (69.6%), ATO (50.6%). Rankings of complete remission are ATRA+RIF (79.3%), ATRA+ATO (64.8%), RIF (60.3%), ATO (55.9%). Rankings of avoiding differentiation syndromes are CT (84...
October 4, 2016: Oncotarget
Osamu Imataki, Makiko Uemura
BACKGROUND: The recent study described a better outcome in acute promyelocytic leukemia patients treated with all-trans retinoic acid and arsenic oxide compared to those treated with all-trans retinoic acid combined with conventional chemotherapy. The pivotal study indicated that favorable-risk acute promyelocytic leukemia patients can be cured without any cytotoxic chemotherapy. Even high-risk patients are treatable with cytotoxic agents. Acute promyelocytic leukemia does not develop only by the dedifferentiation caused by PML-RARA...
2016: BMC Clinical Pathology
Masamitsu Yanada, Shingo Yano, Heiwa Kanamori, Moritaka Gotoh, Nobuhiko Emi, Kyoko Watakabe, Mineo Kurokawa, Akinori Nishikawa, Takehiko Mori, Naoto Tomita, Makoto Murata, Hisako Hashimoto, Hideho Henzan, Yoshinobu Kanda, Masashi Sawa, Akio Kohno, Yoshiko Atsuta, Tatsuo Ichinohe, Akiyoshi Takami
We conducted a retrospective registry-based study involving 198 patients with acute promyelocytic leukemia (APL) who underwent autologous hematopoietic cell transplantation (HCT) during second complete remission (CR2) from 1995 to 2012. Arsenic trioxide (ATO) became commercially available in Japan in December 2004, and a substantial increase in the annual numbers of transplantations has occurred since 2005. Patients transplanted after 2006 had significantly better relapse-free and overall survival than those transplanted before 2004 (p = ...
October 5, 2016: Leukemia & Lymphoma
Erin Damery, Dominic A Solimando, J Aubrey Waddell
The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr., President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast...
September 2016: Hospital Pharmacy
Jaime A Campbell, John R Krause
Prolonged immunosuppression in solid organ transplant recipients has been considered a risk for developing opportunistic infections and malignancies. Acute leukemia is a rare complication. We report a case of acute promyelocytic leukemia (APL) (FAB M3) after cadaveric renal transplant for focal segmental glomerulosclerosis in a 24-year-old woman. Her immunosuppressive therapy included tacrolimus, mycophenolate mofetil, and prednisone. Approximately 2 years after transplant, she became pancytopenic, prompting administration of filgrastim...
October 2016: Proceedings of the Baylor University Medical Center
Lisa M Blackburn, Nicole Bauchmire, Sarah Bender, Kelly Tomlinson-Pinkham, Scott Roberts, Sherry Rosan
BACKGROUND: Acute promyelocytic leukemia (APL), once the most lethal form of adult acute leukemia, has become the most curable. The goal of early and well-managed treatment induction is to reduce the malignant burden of promyelocytes to below the cytologically detectable level. OBJECTIVES: Oncology nurses who care for patients with APL need to be acutely aware of the basic differences in this disease from other forms of leukemia, including the two main complications for the newly diagnosed patient...
October 1, 2016: Clinical Journal of Oncology Nursing
Lei Shi, Xiang-Qin Weng, Yan Sheng, Jing Wu, Ming Ding, Xun Cai
Although all-trans retinoic acid (ATRA) is regarded as a prominent example of differentiation therapy, it is not effective for the treatment of other subtypes of acute myeloid leukemia (AML) beyond acute promyelocytic leukemia (APL). Therefore, new strategies need to be explored to extend the efficacy of ATRA-based therapy to non-APL AML patients. In the present study, staurosporine, a protein kinase C (PKC) pan-inhibitor, exhibited synergism with ATRA to promote granulocytic differentiation in poorly ATRA-sensitive U937 cells but not in ATRA unresponsive K562 and Kasumi cells...
September 23, 2016: Oncology Reports
Matthew Dolan, Christine Ngaruiya
BACKGROUND: Acute promyelocytic leukemia (APL) is a rare but particularly malignant form of acute leukemia that is characterized by a rapid progression to fatal hemorrhage. Survival rates of patients with APL have increased with the introduction of all-trans retinoic acid (ATRA), but early deaths caused by hemorrhage still persist. CASE REPORT: A man with undiagnosed APL presenting with focal neurologic findings and deteriorating altered mental status caused by an intracranial hemorrhage is discussed...
September 19, 2016: Journal of Emergency Medicine
Anna Maria Testi, Maria Luisa Moleti, Martina Canichella, Sara Mohamed, Daniela Diverio, Maria Stefania de Propris, Franco Locatelli, Francesco Lo Coco, Robin Foà
No abstract text is available yet for this article.
September 23, 2016: Leukemia & Lymphoma
Yingmei Zhang, Jinxiao Hou, Fei Ge, Fenglin Cao, Haitao Li, Ping Wang, Mengyuan Xu, Peng Song, Xiaoxia Li, Shuye Wang, Jinmei Li, Xueying Han, Yanhong Zhao, Yanhua Su, Yinghua Li, Shengjin Fan, Limin Li, Jin Zhou
The pathogenesis of therapy-induced differentiation syndrome (DS) in patients with acute promyelocytic leukemia (APL) remains unclear. In this study, mRNA and microRNA (miRNA) expression profiling of peripheral blood APL cells from patients complicated with vs. without DS were integratively analyzed to explore the mechanisms underlying arsenic trioxide treatment-associated DS. By integrating the differentially expressed data with the data of differentially expressed microRNAs and their computationally predicted target genes, as well as the data of transcription factors and differentially expressed target microRNAs obtained from a literature search, a DS-related genetic regulatory network was constructed...
September 13, 2016: Oncotarget
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