A Six Gene Expression Signature Defines Aggressive Subtypes and Predicts Outcome in Childhood and Adult Acute Lymphoblastic Leukemia

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 May 23

PMID 26001296

Citations 27

Authors

Jin Wang

Jian-Qing Mi

Alexandra Debernardi

Anne-Laure Vitte

Anouk Emadali

Julia A Meyer

Konstantina Charmpi

Bernard Ycart

Mary B Callanan

William L Carroll

Saadi Khochbin

Sophie Rousseaux

Affiliations

Soon will be listed here.

Abstract

Abnormal gene expression in cancer represents an under-explored source of cancer markers and therapeutic targets. In order to identify gene expression signatures associated with survival in acute lymphoblastic leukemia (ALL), a strategy was designed to search for aberrant gene activity, which consists of applying several filters to transcriptomic datasets from two pediatric ALL studies. Six genes whose expression in leukemic blasts was associated with prognosis were identified:three genes predicting poor prognosis (AK022211, FASTKD1 and STARD4) and three genes associated with a favorable outcome (CAMSAP1, PCGF6 and SH3RF3). Combining the expression of these 6 genes could successfully predict prognosis not only in the two discovery pediatric ALL studies, but also in two independent validation cohorts of adult patients, one from a publicly available study and one consisting of 62 newly recruited Chinese patients. Moreover, our data demonstrate that our six gene based test is particularly efficient in stratifying MLL or BCR.ABL negative patients. Finally, common biological traits characterizing aggressive forms of ALL in both children and adults were found, including features of dormant hematopoietic stem cells, suggesting new therapeutic strategies.

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