Expression of BCR/ABL p210 from a Knockin Allele Enhances Bone Marrow Engraftment without Inducing Neoplasia

Samantha B. Foley, Zacariah L. Hildenbrand, Abigail A. Soyombo, Jeffery A. Magee, Yipin Wu, Katherine I. Oravecz-Wilson, Theodora S. Ross

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22 Scopus citations

Abstract

Chronic myeloid leukemia (CML) and some acute lymphoblastic leukemias are characterized by the t(9;22) chromosome, which encodes the BCR/ABL oncogene. Multiple mouse models of CML express BCR/ABL at high levels from non-. Bcr promoters, resulting in the development of leukemias. In contrast, a significant fraction of healthy humans have been found to have BCR/ABL-positive hematopoietic cells. To bridge the gap between the information derived from current mouse models and nonleukemic humans with the BCR/ABL oncogene, we generated a knockin model with BCR/ABL p210 expressed from the Bcr locus. Unlike previous models, expression of BCR/ABL from the knockin allele did not induce leukemia. BCR/ABL mutant cells did exhibit favorable bone marrow engraftment compared to control cells. These data suggest that BCR/ABL expression alone is insufficient to induce disease. This model allows for inducible spatial and temporal control of BCR/ABL expression for analysis of early steps in the pathogenesis of BCR/ABL-expressing leukemias

Original languageEnglish
Pages (from-to)51-60
Number of pages10
JournalCell Reports
Volume5
Issue number1
DOIs
StatePublished - Oct 17 2013
Externally publishedYes

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    Foley, S. B., Hildenbrand, Z. L., Soyombo, A. A., Magee, J. A., Wu, Y., Oravecz-Wilson, K. I., & Ross, T. S. (2013). Expression of BCR/ABL p210 from a Knockin Allele Enhances Bone Marrow Engraftment without Inducing Neoplasia. Cell Reports, 5(1), 51-60. https://doi.org/10.1016/j.celrep.2013.08.037