Project description:Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17) leading to formation of PML-RARA fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, while mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large scale activation of gene expression and reduced in vitro differentiation potential.

2016-02-17 | GSE77946 | GEO

Evolution of a FLT3-TKD mutated subclone at meningeal relapse in acute promyelocytic leukemia.

Project description: Not available

| S-EPMC5002926 | biostudies-literature

Genomic Profiling of Pediatric Acute Myeloid Leukemia Reveals a Changing Mutational Landscape from Disease Diagnosis to Relapse.

Project description: Not available

| S-EPMC4873364 | biostudies-literature

The molecular landscape of ETMR at diagnosis and relapse.

Project description: Not available

| S-EPMC6908757 | biostudies-literature

The Molecular Landscape of ETMR at Diagnosis and Relapse

Project description:This SuperSeries is composed of the SubSeries listed below.