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Medline ® Abstract for Reference 13

of 'Cellular and molecular biology of chronic myeloid leukemia'

BCR-ABL-transformed GMP as myeloid leukemic stem cells.
Minami Y, Stuart SA, Ikawa T, Jiang Y, Banno A, Hunton IC, Young DJ, Naoe T, Murre C, Jamieson CH, Wang JY
Proc Natl Acad Sci U S A. 2008;105(46):17967. Epub 2008 Nov 11.
During blast crisis of chronic myelogenous leukemia (CML), abnormal granulocyte macrophage progenitors (GMP) with nuclear beta-catenin acquire self-renewal potential and may function as leukemic stem cells (Jamieson et al. N Engl J Med, 2004). To develop a mouse model for CML-initiating GMP, we expressed p210(BCR-ABL) in an established line of E2A-knockout mouse BM cells that retain pluripotency in ex vivo culture. Expression of BCR-ABL in these cells reproducibly stimulated myeloid expansion in culture and generated leukemia-initiating cells specifically in the GMP compartment. The leukemogenic GMP displayed higher levels of beta-catenin activity than either the nontransformed GMP or the transformed nonGMP, both in culture and in transplanted mouse BM. Although E2A-deficiency may have contributed to the formation of leukemogenic GMP, restoration of E2A-function did not reverse BCR-ABL-induced transformation. These results provide further evidence that BCR-ABL-transformed GMP with abnormal beta-catenin activity can function as leukemic stem cells.
Division of Hematology-Oncology, Department of Medicine, University of California at San Diego School of Medicine, La Jolla, CA 92093-0820, USA.