Cellular Expression of Antiapoptotic BCL-2 Oncoprotein in Newly Diagnosed Childhood Acute Lymphoblastic Leukemia: A Children's Cancer Group Study

Author:

Uckun Fatih M.1,Yang Zhiwen1,Sather Harland1,Steinherz Peter1,Nachman James1,Bostrom Bruce1,Crotty Lisa1,Sarquis Mireille1,Ek Onur1,Zeren Tamer1,Tubergen David1,Reaman Gregory1,Gaynon Paul1

Affiliation:

1. From the Children's Cancer Group ALL Biology Reference Laboratory and Biotherapy Institute, University of Minnesota, Roseville, MN; Memorial Sloan-Kettering Cancer Center, New York, NY; Statistics and Data Center, Group Operations Office of the Children's Cancer Group, Arcadia, CA; University of Chicago, Chicago, IL; M.D. Anderson Cancer Center, Houston, TX; George Washington University Medical Center, Washington, DC; and the University of Wisconsin, Madison, WI.

Abstract

We found a marked variation in BCL-2 oncoprotein expression levels of primary leukemic cells from 338 children with newly diagnosed acute lymphoblastic leukemia (ALL). None of the high-risk features predictive of poor treatment outcome in childhood ALL, such as older age, high white blood cell (WBC) count, organomegaly, T-lineage immunophenotype, ability of leukemic cells to cause overt leukemia in severe combined immunodeficient (SCID) mice, presence of MLL-AF4, and BCR-ABL fusion transcripts were associated with high levels of BCL-2 expression. Overall, high BCL-2 levels were not associated with slow early response, failure to achieve complete remission, or poor event-free survival. High BCL-2 levels in primary leukemic cells predicted slow early response only in T-lineage ALL patients, which comprised approximately 15% of the total patient population. Even for this small subset of patients, the level of BCL-2 expression did not have a significant impact on the short-term event-free survival.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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