Bcr-Abl has a greater intrinsic capacity than v-Abl to induce the neoplastic expansion of myeloid cells

The Bcr-Abl/p210 fusion protein plays a primary role in the pathogenesis of chronic myelogenous leukemia (CML), Abelson murine leukemia virus, which e ncodes v-Abl/p160, induces a pre-B cell leukemia/lymphoma in mice. It has b een unclear whether the apparent specificity of these two abl oncogenes for myeloid versus lymphoid neoplasms is due to specific intrinsic properties of these Abl oncoproteins, or due to the properties of the target cells exp ressing them. We have recently shown that expression of Bcr-Abl in bone mar row cells by retroviral transduction efficiently induces a myeloproliferati ve disorder in mice resembling human CML, In this study, we compared Ber-Ab l/p210 and v-Abl/p160 in this mouse CML model. We found that early in the c ourse of disease, both Bcr-Abl/p210 and v-Abl/p160 expanded early immature hematopoietic cells. Later Bcr-Abl/p210 selectively expanded myeloid cells while v-Abl/p160 primarily induced the rapid in vivo expansion of B lymphob lastic cells, along with a minor population of myeloid cells. In vitro, Bcr -Abl/p210 induced more growth of myeloid colonies from S-fluorouracil treat ed bone marrow than v-Abl/p160. These results, obtained under equal bone ma rrow transduction/transplantation conditions, indicate that Bcr-Abl/p210 ha s a greater intrinsic capacity than v-Abl/pl60 to induce the neoplastic gro wth of myeloid cells. In addition, we found that cultured cells expressing Bcr-Abl/p210 had more activated STAT5 than cells that expressed v-Abl/p160. This suggests that activation of STAT5 might be one part of the mechanism of abl oncogene disease specificity.