Initiating and Cancer-Propagating Cells in <i>TEL-AML1</i> -Associated Childhood Leukemia

Dengli Hong(Institute of Cancer Research), Rajeev Gupta(Institute of Cancer Research), Philip Ancliff(Institute of Cancer Research), Ann Atzberger(Institute of Cancer Research), John Brown(Institute of Cancer Research), Shamit Soneji(Institute of Cancer Research), Joanne Green(Institute of Cancer Research), Sue Colman(Institute of Cancer Research), Wanda Piacibello(Institute of Cancer Research), Veronica J. Buckle(Institute of Cancer Research), Shinobu Tsuzuki(Institute of Cancer Research), Mel Greaves(Institute of Cancer Research), Tariq Enver(Institute of Cancer Research)
Science
January 17, 2008
10.1126/science.1150648
Cited by 388

Abstract

Understanding cancer pathogenesis requires knowledge of not only the specific contributory genetic mutations but also the cellular framework in which they arise and function. Here we explore the clonal evolution of a form of childhood precursor-B cell acute lymphoblastic leukemia that is characterized by a chromosomal translocation generating a TEL-AML1 fusion gene. We identify a cell compartment in leukemic children that can propagate leukemia when transplanted in mice. By studying a monochorionic twin pair, one preleukemic and one with frank leukemia, we establish the lineal relationship between these "cancer-propagating" cells and the preleukemic cell in which the TEL-AML1 fusion first arises or has functional impact. Analysis of TEL-AML1-transduced cord blood cells suggests that TEL-AML1 functions as a first-hit mutation by endowing this preleukemic cell with altered self-renewal and survival properties.

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