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Promyelocytic leukemia

Lianlian Li, Yong Wang, Xiaoyu Zhang, Guanhua Song, Qiang Guo, Zhiyong Zhang, Yutao Diao, Haipeng Yin, Hongyan Liu, Guosheng Jiang
All-trans retinoic acid (ATRA) has been used for the treatment of acute promyelocytic leukemia (APL). However, its molecular mechanisms of action are unclear. Ubiquitin-specific protease 48 (USP48) is a deubiquitinase enzyme that can post-translationally remove ubiquitin molecules from substrates. In the present study, the role of USP48 in ATRA-induced differentiation of APL cells was studied. The expression of USP48 decreased following ATRA treatment. Functionally, overexpression of USP48 using electroporation-mediated delivery inhibited the proliferation of APL cells and promoted ATRA-mediated differentiation...
June 13, 2018: International Journal of Oncology
Peter Geon Kim, Kelly Bridgham, Evan C Chen, Mahesh K Vidula, Olga Pozdnyakova, Andrew M Brunner, Amir T Fathi
The use of all-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) with or without cytotoxic chemotherapy is highly effective in acute promyelocytic leukemia (APL) but incident chronic adverse events (AEs) after initiation of therapy are not well understood. We retrospectively analyzed adult patients with newly diagnosed APL from 2004 through 2014 to identify incident AEs following treatment and contributing risk factors. Cardiac and neurologic AEs were more common and characterized in detail. Cardiac AEs such as the development of coronary artery disease (CAD), arrhythmias, and heart failure had a cumulative incidence of 6...
2018: Leukemia Research Reports
Daria Gaut, Joshua Sasine, Gary Schiller
Although rare, secondary clonal hematologic neoplasia may occur after successful therapy for acute promyelocytic leukemia (APL). These secondary clonal events may be considered therapy-related, but may also be due to an underlying background of clonal hematopoiesis from which both malignancies may develop. In this manuscript, we describe two patients with secondary clones after APL therapy characterized in one patient by deletion of chromosome 11q23 and, in the other, by monosomy of chromosome 7, and also provide a review of all secondary clonal disorders described after APL therapy...
2018: Leukemia Research Reports
Carmen Winters, Andy I Chen, Stephen Moore, Elie Traer, Jennifer Dunlap
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia defined by a balanced translocation between chromosomes 15 and 17 resulting in fusion of the promyelocytic leukemia gene (PML) on chromosome 15 with the retinoic acid receptor-alpha gene (RARα) on chromosome 17. APL often presents with pancytopenia and is associated with a life threatening coagulopathy making prompt diagnosis and initiation of therapy critical. We report an unusual case of APL in a 59 year old female without peripheral blood abnormalities or diffuse marrow involvement...
2018: Leukemia Research Reports
Christopher A Miller, Christopher Tricarico, Zachary L Skidmore, Geoffrey L Uy, Yi-Shan Lee, Anjum Hassan, Michelle D O'Laughlin, Heather Schmidt, Ling Tian, Eric J Duncavage, Malachi Griffith, Obi L Griffith, John S Welch, Lukas D Wartman
No abstract text is available yet for this article.
June 12, 2018: Blood Advances
András Demjén, Róbert Alföldi, Anikó Angyal, Márió Gyuris, László Hackler, Gábor J Szebeni, János Wölfling, László G Puskás, Iván Kanizsai
The synthesis and in vitro cytotoxic characteristics of new imidazo[1,2-b]pyrazole-7-carboxamides were investigated. Following a hit-to-lead optimization exploiting 2D and 3D cultures of MCF-7 human breast, 4T1 mammary gland, and HL-60 human promyelocytic leukemia cancer cell lines, a 67-membered library was constructed and the structure-activity relationship (SAR) was determined. Seven synthesized analogues exhibited sub-micromolar activities, from which compound 63 exerted the most significant potency with a remarkable HL-60 sensitivity (IC50  = 0...
June 10, 2018: Archiv der Pharmazie
Christian Hoischen, Shamci Monajembashi, Klaus Weisshart, Peter Hemmerich
The promyelocytic leukemia ( pml ) gene product PML is a tumor suppressor localized mainly in the nucleus of mammalian cells. In the cell nucleus, PML seeds the formation of macromolecular multiprotein complexes, known as PML nuclear bodies (PML NBs). While PML NBs have been implicated in many cellular functions including cell cycle regulation, survival and apoptosis their role as signaling hubs along major genome maintenance pathways emerged more clearly. However, despite extensive research over the past decades, the precise biochemical function of PML in these pathways is still elusive...
2018: Frontiers in Oncology
Abhishek A Singh, Francesca Petraglia, Angela Nebbioso, Guoqiang Yi, Mariarosaria Conte, Sergio Valente, Amit Mandoli, Lucia Scisciola, Rik Lindeboom, Hinri Kerstens, Eva M Janssen-Megens, Farzin Pourfarzad, Ehsan Habibi, Kim Berentsen, Bowon Kim, Colin Logie, Simon Heath, Albertus T J Wierenga, Laura Clarke, Paul Flicek, Joop H Jansen, Taco Kuijpers, Marie Laure Yaspo, Veronique Della Valle, Olivier Bernard, Ivo Gut, Edo Vellenga, Hendrik G Stunnenberg, Antonello Mai, Lucia Altucci, Joost H A Martens
Epigenomic alterations have been associated with both pathogenesis and progression of cancer. Here, we analyzed the epigenome of two high-risk APL (hrAPL) patients and compared it to non-high-risk APL cases. Despite the lack of common genetic signatures, we found that human hrAPL blasts from patients with extremely poor prognosis display specific patterns of histone H3 acetylation, specifically hyperacetylation at a common set of enhancer regions. In addition, unique profiles of the repressive marks H3K27me3 and DNA methylation were exposed in high-risk APLs...
May 22, 2018: Oncotarget
Nathaniel J Buteyn, Kavin Fatehchand, Ramasamy Santhanam, Huiqing Fang, Gino M Dettorre, Shalini Gautam, Bonnie K Harrington, Sally E Henderson, Giovanna Merchand-Reyes, Xiaokui Mo, Don M Benson, William E Carson, Sumithira Vasu, John C Byrd, Jonathan P Butchar, Susheela Tridandapani
Acute myeloid leukemia (AML) remains a significant health problem, with poor outcomes despite chemotherapy and bone-marrow transplants. Although one form of AML, acute promyelocytic leukemia (APL), is successfully treated with all-trans retinoic acid (ATRA), this drug is seemingly ineffective against all other forms of AML. Here, we show that ATRA upregulates CD38 expression on AML blasts to sufficient levels that promote antibody-mediated fratricide following the addition of anti-CD38 Daratumumab. The combination of ATRA plus Daratumumab induced Fc-dependent conjugate formation and cytotoxicity among AML blasts in vitro...
June 2, 2018: International Immunology
Jing-Yi Zhang, Min Wang, Rui-Ying Wang, Xiao Sun, Yu-Yang Du, Jing-Xue Ye, Gui-Bo Sun, Xiao-Bo Sun
Arsenic trioxide (ATO) is used as a therapeutic agent in the treatment of acute promyelocytic leukemia (APL). The therapeutic use of arsenic is limited due to its severe cardiovascular side effects. The cardio-protective effect of salvianolic acid A (Sal A) against ATO cardiotoxicity has been reported. However, the distinct role of the mitochondria in the cardio-protection of Sal A is not understood. The aim of this study was to determine whether Sal A preconditioning protects against ATO-induced heart injury by maintaining cardiac mitochondrial function and biogenesis...
2018: Frontiers in Pharmacology
Eduarda Fratoni, Amanda Ellen de Athayde, Marina da Silva Machado, Tailyn Zermiani, Ivonilce Venturi, Matheus Corrêa Dos Santos, Fabiane Lobato, Valdir Cechinel Filho, Gilberto Carlos Franchi, Alexandre Eduardo Nowill, José Roberto Santin, Angela Malheiros
Stem barks of Drimys brasiliensis (Winteraceae) are consumed by the population in the form of a condiment. It is widely used to treat gastric and stomach problems and also to treat cancer. The extracts have demonstrated antiproliferative, antileishmanial and antimicrobial activities assigned to drimane sesquiterpenes. This study aimed to optimize the extraction conditions of the drimanes sesquiterpenes identified as 1-β-(p-coumaroyloxy)-polygodial 1, drimanial 2 and 1-β-(p-methoxycinnamoyl)-polygodial 3 in stem bark extracts...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yinjun Lou, Ying Lu, Zhijuan Zhu, Yafang Ma, Shanshan Suo, Yungui Wang, Dong Chen, Hongyan Tong, Wenbin Qian, Haitao Meng, Wenyuan Mai, Wenjun Yu, Weilai Xu, Lei Wang, Liping Mao, Renzhi Pei, Jie Jin
Limited data was available for long-term follow-up in newly diagnosed acute promyelocytic leukemia (APL) patients treated with all-trans-retinoic acid (ATRA) plus intravenously arsenic trioxide (ATO)-based front-line therapy. The aim of this work was to retrospectively analyze the long-term survival rate and frequency of therapy-related myeloid neoplasia (t-MN) occurring in a large cohort of APL patients. A total of 760 newly diagnosed patients with APL between January 1999 and May 2016 were evaluated. The early death rate was 9...
June 3, 2018: Hematological Oncology
Hideaki Kato, Hiroyuki Fujita, Nobu Akiyama, Shun-Ichi Kimura, Nobuhiro Hiramoto, Naoko Hosono, Tsutomu Takahashi, Kazuyuki Shigeno, Hitoshi Minamiguchi, Junichi Miyatake, Hiroshi Handa, Yoshinobu Kanda, Minoru Yoshida, Shuichi Miyawaki, Shigeki Ohtake, Tomoki Naoe, Hitoshi Kiyoi, Itaru Matsumura, Yasushi Miyazaki
PURPOSE: The Japan Adult Leukemia Study Group (JALSG) AML201 protocols are regimens for remission induction and consolidation chemotherapy of acute myeloid leukemia (AML) and have been widely accepted in Japan since 2001. Management of infectious complications during chemotherapy has a key role in the supportive care of AML patients. METHODS: By using case report forms collected in December 2001 and December 2005, we retrospectively analyzed the infectious complications in adult patients treated by using the JALSG AML201 protocols against AML (excluding promyelocytic leukemia)...
June 2, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Maiara de Souza Oliveira, Ádila Angélica Dantas de Santana, Rodrigo S Correa, Milena Botelho Pereira Soares, Alzir Azevedo Batista, Daniel Pereira Bezerra
Ruthenium-based compounds represent a class of potential antineoplastic drugs. Recently, we designed, synthesized, and identified the Ru(II)-thymine complex [Ru(PPh₃)₂(Thy)(bipy)]PF₆ (where PPh = triphenylphosphine, Thy = thymine and bipy = 2,2'-bipyridine) as a potent cytotoxic agent with the ability to bind to DNA and human and bovine serum albumins. In this study, the underlying cytotoxic mechanism of the [Ru(PPh₃)₂(Thy)(bipy)]PF₆ complex was assessed. This complex displayed potent cytotoxicity in different cancer cell lines; the morphology that is associated with apoptotic cell death, increased internucleosomal DNA fragmentation without cell membrane permeability, loss of the mitochondrial transmembrane potential, increased phosphatidylserine externalization, and caspase-3 activation were observed in human promyelocytic leukemia HL-60 cells that were treated with the complex...
May 30, 2018: International Journal of Molecular Sciences
Xiaolan Lian, Yu-Min Lin, Shingo Kozono, Megan K Herbert, Xin Li, Xiaohong Yuan, Jiangrui Guo, Yafei Guo, Min Tang, Jia Lin, Yiping Huang, Bixin Wang, Chenxi Qiu, Cheng-Yu Tsai, Jane Xie, Ziang Jeff Cao, Yong Wu, Hekun Liu, Xiaozhen Zhou, Kunping Lu, Yuanzhong Chen
BACKGROUND: The increasing genomic complexity of acute myeloid leukemia (AML), the most common form of acute leukemia, poses a major challenge to its therapy. To identify potent therapeutic targets with the ability to block multiple cancer-driving pathways is thus imperative. The unique peptidyl-prolyl cis-trans isomerase Pin1 has been reported to promote tumorigenesis through upregulation of numerous cancer-driving pathways. Although Pin1 is a key drug target for treating acute promyelocytic leukemia (APL) caused by a fusion oncogene, much less is known about the role of Pin1 in other heterogeneous leukemia...
May 30, 2018: Journal of Hematology & Oncology
Kazuyuki Sato, Hirotaka Sakai, Yusuke Saiki, Akiko Uchida, Yu Uemura, Satoshi Yokoi, Yuka Tsuruoka, Yuji Nishio, Manabu Matsunawa, Yoshinori Suzuki, Yasushi Isobe, Masayuki Kato, Naoto Tomita, Yasuyuki Inoue, Ikuo Miura
The introduction of all-trans retinoic acid (ATRA) has made acute promyelocytic leukemia (APL) a curable disease; however, early death prior to the completion of treatment remains a problem. In quantitative evaluation of response to ATRA treatment, lymphocytes must be excluded as they do not originally have t(15;17). We categorized peripheral blood leukocytes by nuclear morphology into polymorphonuclear cells (PMNs) comprising segmented granulocytes, and non-polymorphonuclear cells (NPMs) which includes lymphocytes, monocytes, band cells, and immature myeloid cells...
May 29, 2018: International Journal of Hematology
Chunlu Gao, Shuang Hu, Meihua Guo, Xin Hai, Jin Zhou
PURPOSE: This study evaluated pharmacokinetics (PK) and safety profiles of single agent arsenic trioxide (ATO, As2 O3 ) administrated as continuous slow-rate infusion in patients with newly diagnosed acute promyelocytic leukemia. PATIENTS AND METHODS: Patients received 0.16 mg/kg ATO per day. ATO was given for 40 min infusion on the first day followed by 18-20 h daily at a very slow rate with infusion speed of 8 drips/min. During the first week, plasma samples were collected immediately before next administration on each day, and 0...
May 29, 2018: Cancer Chemotherapy and Pharmacology
Shufen Li, Yunlin Ma, Yun Tan, Xuefei Ma, Ming Zhao, Bing Chen, Rongsheng Zhang, Zhu Chen, Kankan Wang
Circular RNAs (circRNAs) are a novel class of powerful regulators in gene expression and participate in the pathogenesis of many diseases, including cancer. However, little is known about the roles of circRNAs in the development and treatment of acute promyelocytic leukemia (APL). Here we report the expression profiling and function of circRNAs in APL, including their dynamic regulation during all-trans retinoic acid (ATRA)-induced differentiation. We performed two independent ribosomal RNA-minus RNA-sequencing (Ribo-minus RNA-seq) experiments with and without RNase R treatment on APL patient-derived NB4 cells and identified a total of 4313 circRNAs, including 1098 newly identified circRNAs...
May 29, 2018: Cell Death & Disease
Jing Fan, Qianjun He, Zhe Wang, Weiren Huang, Zhiming Cai
The synergistic effect of arsenic (As) and all-trans retinoic acid in acute promyelocytic leukemia (APL) has been well documented. However, several major issues impeding the efficient delivery of these drugs for APL therapy remain unsolved. The low solubility of retinoic acid in physiological solutions makes drug delivery cumbersome, and the high systemic cytotoxicity of arsenic trioxide leads to unwanted side effects. In the present study, a new organo-arsenic molecule was synthesized via template-directed ring-opening esterification of an epoxy arsenic hydride (2-chloro-1,3,2-dioxaarsolane, CDA) under a nucleophilic attack exposing the hydroxyl terminus...
June 1, 2018: Journal of Biomedical Nanotechnology
Andrea Flores Burroughs, Sylvia Eluhu, Diva Whalen, J Shawn Goodwin, Amos M Sakwe, Ifeanyi J Arinze
BACKGROUND/AIMS: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a basic leucine-zipper transcription factor essential for cellular responses to oxidative stress. Degradation of Nrf2 in the cytoplasm, mediated by Keap1-Cullin3/RING box1 (Cul3-Rbx1) E3 ubiquitin ligase and the proteasome, is considered the primary pathway controlling the cellular abundance of Nrf2. Although the nucleus has been implicated in the degradation of Nrf2, little information is available on how this compartment participates in degrading Nrf2...
May 22, 2018: Cellular Physiology and Biochemistry
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