Significance of Inactivated Genes in Leukemia: Pathogenesis and Prognosis

(Pages: 9-26)
Nazanin Heidari, M.Sc, 1Saeid Abroun, Ph.D, 2Jessika Bertacchini, Ph.D, 3Tina Vosoughi, M.D, 1Fakher Rahim, Ph.D, 1Najmaldin Saki, Ph.D, 1,*
Health Research Institute, Thalassemia and Hemoglobinopathy Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Signal Transduction Unit, Department of Surgery, Medicine, Dentistry and Morphology, University of Modena and Reggio Emilia, Modena, Italy
Health Research Institute, Thalassemia and Hemoglobinopathy Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Signal Transduction Unit, Department of Surgery, Medicine, Dentistry and Morphology, University of Modena and Reggio Emilia, Modena, Italy
*Corresponding Address: Health Research Institute Thalassemia and Hemoglobinopathy Research Center Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran Email:najmaldinsaki@gmail.com
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Heidari Nazanin, Abroun Saeid, Bertacchini Jessika, Vosoughi Tina, Rahim Fakher, Saki Najmaldin. Significance of Inactivated Genes in Leukemia: Pathogenesis and Prognosis. Cell J. 2017; 19(Suppl 1): 9-26.

Abstract

Epigenetic and genetic alterations are two mechanisms participating in leukemia, which can inactivate genes involved in leukemia pathogenesis or progression. The purpose of this review was to introduce various inactivated genes and evaluate their possible role in leukemia pathogenesis and prognosis. By searching the mesh words “Gene, Silencing AND Leukemia” in PubMed website, relevant English articles dealt with human subjects as of 2000 were included in this study. Gene inactivation in leukemia is largely mediated by promoter’s hypermethylation of gene involving in cellular functions such as cell cycle, apoptosis, and gene transcription. Inactivated genes, such as ASPP1, TP53, IKZF1 and P15, may correlate with poor prognosis in acute lymphoid leukemia (ALL), chronic lymphoid leukemia (CLL), chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML), respectively. Gene inactivation may play a considerable role in leukemia pathogenesis and prognosis, which can be considered as complementary diagnostic tests to differentiate different leukemia types, determine leukemia prognosis, and also detect response to therapy. In general, this review showed some genes inactivated only in leukemia (with differences between B-ALL, T-ALL, CLL, AML and CML). These differences could be of interest as an additional tool to better categorize leukemia types. Furthermore; based on inactivated genes, a diverse classification of Leukemias could represent a powerful method to address a targeted therapy of the patients, in order to minimize side effects of conventional therapies and to enhance new drug strategies.

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