Ikaros mutation confers integrin-dependent pre-B cell survival and progression to acute lymphoblastic leukemia

ABSTRACT: Deletion of the Ikaros DNA-binding domain generates dominant-negative isoforms that interfere with Ikaros family activity and correlate with poor prognosis in human precursor B cell acute lymphoblastic leukemias (B-ALL).  Here, we show that conditional inactivation of the Ikaros DNA binding domain in early pre-B cells arrests their differentiation at a stage where integrin-dependent niche adhesion augments mitogen-activated protein kinase signaling, proliferation, and self-renewal, and attenuates pre-B cell receptor signaling and differentiation. Transplantation of polyclonal Ikzf1 mutant pre-B cells results in long-latency oligoclonal pre-B-ALL, demonstrating that loss of Ikaros contributes to multistep B-leukemogenesis. These results explain how normal pre-B cells transit from a highly p

ORGANISM(S): Mus musculus

SUBMITTER: Katia Georgopoulos 

PROVIDER: E-GEOD-53401 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress