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Acute promyelocyte leukemia

Can Chen, Xilian Huang, Kaile Wang, Kuang Chen, Danquan Gao, Shenxian Qian
Acute promyelocytic leukemia (APL) is a rare leukemia characterized by the balanced reciprocal translocation between the promyelocytic leukemia gene on chromosome 15 and the retinoic acid receptor α (RARα) gene on chromosome 17, and accounts for 10-15% of newly diagnosed acute myeloid leukemia each year. The combined use of all-trans retinoic acid and arsenic trioxide (ATO) as primary therapy has markedly improved the survival rate of patients with APL. Mortality in the first 30 days following therapy remains a major contribution to treatment failure...
April 2018: Oncology Letters
Mona Dawood, Sami Hamdoun, Thomas Efferth
Arsenic trioxide is a traditional remedy in Chinese Medicine since ages. Nowadays, it is clinically used to treat acute promyelocytic leukemia (APL) by targeting PML/RARA. However, the drug's activity is broader and the mechanisms of action in other tumor types remain unclear. In this study, we investigated molecular modes of action by classical and network pharmacological approaches. CEM/ADR5000 resistance leukemic cells were similar sensitive to As2 O3 as their wild-type counterpart CCRF-CEM (resistance ratio: 1...
2018: Frontiers in Pharmacology
Nicoletta Coccaro, Antonella Zagaria, Paola Orsini, Luisa Anelli, Giuseppina Tota, Paola Casieri, Luciana Impera, Angela Minervini, Crescenzio F Minervini, Cosimo Cumbo, Elisa Parciante, Anna Mestice, Mario Delia, Claudia Brunetti, Giorgina Specchia, Francesco Albano
Most Acute Promyelocytic Leukemia (APL) patients express PML-RARA fusion; in rare cases RARA is rearranged with partner genes other than PML. To date, only two patients presenting features similar to APL showing the RARG gene rearrangement have been described. We report an Acute Myeloid Leukemia (AML) patient with morphology resembling APL without involvement of the RARA gene. Molecular and Fluorescent In Situ Hybridization (FISH) analyses excluded PML-RARA fusion and variant rearrangements involving RARA and RARG loci...
March 9, 2018: Human Pathology
Hayeon Baik, Mathias Boulanger, Moshen Hosseini, Julie Kowalczyk, Sonia Zaghdoudi, Tamara Salem, Jean Emmanuel Sarry, Yosr Hicheri, Guillaume Cartron, Marc Piechaczyk, Guillaume Bossis
Differentiation therapies using all-trans retinoic acid (ATRA) are highly efficient at treating acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML). However, their efficacy, if any, is limited in the case of non-APL AML. We report here that inhibition of SUMOylation, a post-translational modification related to ubiquitination, restores the pro-differentiation and anti-proliferative activities of retinoids in non-APL AML. Controlled inhibition of SUMOylation with pharmacological inhibitors 2-D08 or anacardic acid, or via overexpression of SENP deSUMOylases, enhanced the ATRA-induced expression of key genes involved in differentiation, proliferation, and apoptosis in non-APL AML cells...
February 27, 2018: Cancer Research
Tianhui Liu, Lijun Wen, Hongjian Yuan, Yi Wang, Li Yao, Yang Xu, Jiannong Cen, Changgeng Ruan, Depei Wu, Suning Chen
No abstract text is available yet for this article.
February 27, 2018: Blood
Danyue Peng, Huifang Wang, Lei Li, Xiao Ma, Ying Chen, Hao Zhou, Yi Luo, Yin Xiao, Lingbo Liu
Leukemia stem cells (LSCs) are responsible for acute myeloid leukemia (AML) chemotherapy resistance and relapse. Here, we discovered that miR-34c-5p, a microRNA central to the senescence regulation network, was significantly down-regulated in AML (non-acute promyelocytic leukemia, non-APL) stem cells compared to that in normal hematopoietic stem cells (HSCs). The lower expression of miR-34c-5p in LSCs was closely correlated to the adverse prognosis and poor responses to therapy of AML patients. Increased miR-34c-5p expression induced LSCs senescence ex vivo, prevented leukemia development and promoted the eradication of LSCs in immune deficient mice...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
José Carlos Jaime-Pérez, José Ramón Padilla-Medina, Lucía Teresa Fernández, José Luis Herrera-Garza, César Homero Gutiérrez-Aguirre, Luz Tarín-Arzaga, David Gómez-Almaguer
INTRODUCTION: The outcomes for adolescents and young adults (AYAs) with acute myeloid leukemia (AML) have been poorly characterized in Hispanics in low- to middle-income countries. The results are influenced by biologic and socioeconomic factors. The clinical paths for AYA patients with AML are reported. PATIENTS AND METHODS: A retrospective analysis of AYA and pediatric AML patients aged 1 to 39 years during 2003 to 2016 from a single reference center in Northeast Mexico treated with a 7+3 standard protocol was performed...
February 8, 2018: Clinical Lymphoma, Myeloma & Leukemia
Serdal Korkmaz
Hyperleukocytosis is defined as a white blood cell count greater than 100.000/μL in patients affected by acute or chronic leukemias. Hyperleukocytosis is more common in acute leukemias than in chronic leukemias. Risk factors include younger age, acute myeloid leukemia, the microgranular variant of acute promyelocytic leukemia, acute lymphoblastic leukemia and some cytogenetic abnormalities. Although it can affect any organ system, symptoms usually arise from involvement of the cerebral, pulmonary and renal microvasculature...
February 20, 2018: Transfusion and Apheresis Science
Jorne Lionel Biccler, Lene Sofie Granfeldt Østgård, Marianne Tang Severinsen, Claus Werenberg Marcher, Peter Møller, Claudia Schöllkopf, Lone Smidstrup Friis, Martin Bøgsted, Lasse Hjort Jakobsen, Tarec Christoffer El-Galaly, Jan Maxwell Nørgaard
No abstract text is available yet for this article.
February 23, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Elodie Collinge, Isabelle Tigaud, Brigitte Balme, Luc-Marie Gerland, Pierre Sujobert, Violette Carlioz, Gilles Salles, Xavier Thomas, Etienne Paubelle
RATIONALE: Acute promyelocytic leukemia (APL) is a curable subtype of acute myeloid leukemia. APL is currently treated with combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) resulting in the induction of apoptosis and differentiation of the leukemic cells. Differentiation syndrome (so-called ATRA syndrome) is the main life-threatening complication of induction therapy with these differentiating agents. PATIENT CONCERNS: Herein, we report the case of a 49-year-old woman diagnosed with APL with, concomitantly, a bulky cutaneous lesion of 10 cm diameter with a red-to-purple background and a necrotic center, localized on her abdomen...
February 2018: Medicine (Baltimore)
Satoshi Koyama, Hiroyuki Fujita, Takeshi Shimosato, Aki Kamijo, Yasufumi Ishiyama, Eri Yamamoto, Yoshimi Ishii, Yukako Hattori, Maki Hagihara, Etsuko Yamazaki, Naoto Tomita, Hideaki Nakajima
Probiotic-rich foods are consumed without much restriction. We report here, a case of septic shock caused by yogurt derived Lactobacillus species in a 54-year-old male patient with acute promyelocytic leukemia, in second complete remission, and who was an autologous stem cell transplantation recipient. He received high dose chemotherapy and autologous peripheral blood stem cell transplantation. He ingested commercially available probiotic-enriched yogurt because of severe diarrhea. One week later, he developed septic shock, and the pathogen was determined by strain-specific PCR analysis as Lactobacillus rhamnosus GG (ATCC 53103), which was found to be identical with the strain in the yogurt he consumed...
February 17, 2018: Probiotics and Antimicrobial Proteins
Xiaolu Song, Ye Peng, Xiaogang Wang, Yirui Chen, Lai Jin, Tianxin Yang, Meihua Qian, Wanmao Ni, Xiangmin Tong, Jianping Lan
BACKGROUND/AIM: As the knowledgebase of acute myeloid leukemia (AML) has grown, classification systems have moved to incorporate these new findings. METHODS: We assessed 32,941 patients with AML whose records are contained in the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Half of all patients diagnosed between 2001 and 2013 did not have a World Health Organization (WHO) classification. Acute promyelocytic leukemia and acute panmyelosis with myelofibrosis were associated with the longest leukemia-specific survival (110 and 115 months, respectively), and AML with minimal differentiation and acute megakaryoblastic leukemia with the shortest (30 and 28 months, respectively)...
February 16, 2018: Acta Haematologica
Jacob T Jackson, Ashley P Ng, Benjamin J Shields, Sue Haupt, Ygal Haupt, Matthew P McCormack
The hematopoietically expressed homeobox (Hhex) transcription factor is overexpressed in human myeloid leukemias. Conditional knockout models of murine acute myeloid leukemia indicate that Hhex maintains leukemia stem cell self-renewal by enabling Polycomb-mediated epigenetic repression of the Cdkn2a tumor suppressor locus, encoding p16 Ink4a and p19 Arf However, whether Hhex overexpression also affects hematopoietic differentiation is unknown. To study this, we retrovirally overexpressed Hhex in hematopoietic progenitors...
February 27, 2018: Blood Advances
Lorena Infante Lara, Sabine Fenner, Steven Ratcliffe, Albert Isidro-Llobet, Michael Hann, Ben Bax, Neil Osheroff
Etoposide and other topoisomerase II-targeted drugs are important anticancer therapeutics. Unfortunately, the safe usage of these agents is limited by their indiscriminate induction of topoisomerase II-mediated DNA cleavage throughout the genome and by a lack of specificity toward cancer cells. Therefore, as a first step toward constraining the distribution of etoposide-induced DNA cleavage sites and developing sequence-specific topoisomerase II-targeted anticancer agents, we covalently coupled the core of etoposide to oligonucleotides centered on a topoisomerase II cleavage site in the PML gene...
February 13, 2018: Nucleic Acids Research
Joanna Roszak, Anna Smok-Pieniążek, Maciej Stępnik
BACKGROUND: Arsenic trioxide (ATO) is a well-recognized antileukemic drug used for the treatment of newly diagnosed and relapsed acute promyelocytic leukemia (APL). A major drawback of therapy with ATO is the development of APL cell resistance, the mechanisms of which are still not clear. OBJECTIVES: The aim of this study was to investigate the role of the PI3K/Akt signaling pathway in ATOtreated human acute myeloid leukemia (HL-60) cells and in ATO-resistant clones...
December 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Wenjun Wu, Xiaoyan Han, Cai Wu, Guoqing Wei, Gaofeng Zheng, Yi Li, Yang Yang, Li Yang, Donghua He, Yi Zhao, Zhen Cai
Acute promyelocytic leukemia (APL) remains a challenge to cure due to the side effects of cytotoxic chemotherapy and drug resistance. The present study demonstrated that vernodalol, an active compound isolated from Centratherum anthelminticum, suppresses APL cell proliferation and induces cell cycle arrest in the G2/M phase through the upregulation of p21 and cell division cycle 25. In addition, vernodalol induced cellular apoptosis via the mitochondrial pathway as observed by the cleavage of caspase-9 as well as the release of cytochrome c and Smac/DIABLO into the cytosol...
February 2018: Oncology Letters
Shousheng Liu, Xiuyu Cai, Liangping Xia, Chang Jiang, Ping Chen, Xiaopai Wang, Bei Zhang, Hong Yun Zhao
Chloroquine (CQ) has been confirmed to exhibit antitumor effects on different types of cancer cell, but whether it exerts the same effect on acute promyelocytic leukemia (APL) cells remains to be confirmed. In the present study, the effects of various concentrations of CQ on the growth, apoptosis and cell cycle distribution of NB4 cells, as well as the potential mechanisms underlying these effects, were examined. The combined effect of CQ and arsenic trioxide (ATO) on the growth of NB4 cells was also determined...
February 2018: Oncology Letters
Kuo-Sheng Hsu, Hung-Ying Kao
Promyelocytic leukemia protein (PML) was originally identified as a fusion partner of retinoic acid receptor alpha in acute promyelocytic leukemia patients with the (15;17) chromosomal translocation, giving rise to PML-RARα and RARα-PML fusion proteins. A body of evidence indicated that PML possesses tumor suppressing activity by regulating apoptosis, cell cycle, senescence and DNA damage responses. PML is enriched in discrete nuclear substructures in mammalian cells with 0.2-1 μm diameter in size, referred to as alternately Kremer bodies, nuclear domain 10, PML oncogenic domains or PML nuclear bodies (NBs)...
2018: Cell & Bioscience
Florian Nolte, Eva Lengfelder, Wolf-Karsten Hofmann
The acute promyelocytic leukemia (APL) is a rare disease. However, if diagnosed early and treated immediately high cure rates can be achieved. Signs of hematopoietic insufficiency such as cytopenias or leucocytosis can be present at first presentation of the patients. Moreover, hemorrhagic diatheses due to coagulpathy are present in approximately 80 % of cases and contribute substatially to the high early death rate in APL patients, which has been reported as high as 30 % in population based studies. In case of initial suspicion of APL treatment with all-trans retinoic acid (ATRA) should be initated immediately to reduce the risk of fatal bleeding events and confirmation or exclusion of the PML-RARA transcript should not be awaited before start of ATRA treatment...
February 2018: Deutsche Medizinische Wochenschrift
Ardeshir Ghavamzadeh, Mahdi Jalili, Sharbanoo Rostami, Marjan Yaghmaie, Leyla Sharifi Aliabadi, Seyed Asadollah Mousavi, Mohammad Vaezi, Hossein Kamranzadeh Fumani, Mohammad Jahani, Kamran Alimoghaddam
BACKGROUND: Acute promyelocytic leukemia (APL) is a curable form of acute myeloid leukemia; in recent years, the use of new treatment strategies, such as combination therapy, have led to improved APL outcomes. Here, outcomes of patients treated with a combination of arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) are compared against patients treated with single ATO therapy. PATIENTS AND METHODS: In total, 67 patients with non-high-risk APL were evaluated...
January 29, 2018: Leukemia Research
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