Elevated expression of a subset of interferon inducible genes in primary bone marrow cells expressing p185 Bcr-Abl versus p210 Bcr-Abl by DNA microarray analysis☆

Abstract 

p185 Bcr-Abl has a more aggressive biological/clinical leukemia phenotype than p210 Bcr-Abl. In this study, we examined differential gene expression using microarrays to determine if upregulation or downregulation of specific genes may explain the distinct phenotypes produced by the two Bcr-Abl forms. RNA was collected from mouse bone marrow mononuclear cells expressing equivalent levels of p185 or p210, and the RNAs were subjected to microarray analysis. Significant differences in gene expression were observed on hierarchical clustering. A group of interferon-γ-inducible genes, including those encoding a family of 47kDa GTPases, were significantly increased in p185 versus p210. This family of GTPases has previously been implicated in interferon-γ-induced resistance against intracellular pathogens, however their exact cellular functions are unknown. Our data suggest that their increased expression may contribute to the biological/clinical phenotype associated with p185.

Abbreviations:  Ph, Philadelphia chromosome, CML, chronic myelogenous leukemia, ALL, acute lymphocytic leukemia, CNL, chronic neutrophilic leukemia, GFP, green fluorescent protein, FACS, fluorescent activated cell sorter

Keywords:  Bcr-Abl, Philadelphia chromosome, Chronic myelogenous leukemia, Acute lymphocytic leukemia, Interferon-γ-inducible GTPases, Microarray analysis