ATG2B (Autophagy-related 2B)

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Title: ATG2B (Autophagy-related 2B)
Author: Bellanné-Chantelot, Christine; Plo, Isabelle
Abstract: Autophagy is a cellular process involved in the sequestration of cytosolic components and their degradation by lysosomes. Autophagy has been involved in physiological responses to stress or aging and in the development of many human diseases including solid and haematological cancers. In humans, 16 autophagy-related genes are known. The ATG2B protein is involved in the late steps of the autophagy process i.e. the formation of autophagosomes that fuse with lysosomes before degradation. Loss-of -function (frameshift) acquired mutations of ATG2B have been identified in gastric and colorectal carcinomas with high microsatellite instability. Both pharmacologic and genetic evidence indicate that autophagy plays pleiotropic functions in hematopoietic cell homeostasis and leukemogeneis. Autophagy could exert two opposite roles (cell death and survival) depending on the nature of the hematopoietic malignancy. The germline duplication of ATG2B and GSKIP, both located in 14q32.2, predisposes to the development of familial myeloproliferative neoplasms with autosomal dominant inheritance, in particular essential thrombocythemia progressing to leukemia. Overexpression of ATG2B and GSKIP enhances megakaryocyte progenitor differentiation by increasing progenitor sensitivity to thrombopoietin. Both genes cooperate with somatic JAK2, MPL and CALR mutations and their overexpression provides a growth advantage to hematopoietic cells carrying these driver mutations that may explain the familial aggregation and the progression of essential thrombocythemia to myelofibrosis and leukemia.
Subject: ATG2B; Myeloproliferative neoplasms (MPN); essential thrombocythemia; myelofibrosis; leukemia; predisposition; ATG2B/GSKIP; chromosome 14; CNV; autophagy; Wnt/beta-catenin pathway; Genes Section; Adolescent; Adult; Aged; Autophagy-Related Proteins; Child; Chromosomes, Human, Pair 14; Female; *Gene Duplication; *Genetic Predisposition to Disease; *Germ Cells; Humans; Induced Pluripotent Stem Cells/cytology; Infant; Leukemia, Myeloid, Acute/*genetics; Male; Myelodysplastic Syndromes/*genetics
Publisher: ARMGHM - Atlas Génétique des Cancers
Date: 2017

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