A six gene expression signature defines aggressive subtypes and predicts outcome in childhood and adult acute lymphoblastic leukemia
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Jin Wang1,2, Jian-Qing Mi1, Alexandra Debernardi2, Anne-Laure Vitte2, Anouk Emadali2, Julia A. Meyer3, Konstantina Charmpi4, Bernard Ycart4, Mary B. Callanan2, William L. Carroll3, Saadi Khochbin2 and Sophie Rousseaux2
1 State Key Laboratory for Medical Genomics and Department of Hematology, Shanghai Institute of Hematology, Collaborative Innovation Center of Systems Biomedicine, Pôle Sino-Français des Sciences du Vivant et Genomique, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2 INSERM, Université Grenoble Alpes, Institut Albert Bonniot, Grenoble, France
3 NYU Cancer Institute, NYU Langone Medical Center, New York, USA
4 Laboratoire Jean Kuntzmann, CNRS, Grenoble, France
Sophie Rousseaux, email:
Saadi Khochbin, email:
Jian-Qing Mi, email:
Keywords: cancer, personalized medicine, risk stratification, minimum residual disease, cancer stem cells
Received: March 15, 2015 Accepted: April 22, 2015 Published: May 12, 2015
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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