Identification of mutations that cooperate with defects in B cell transcription factors to initiate leukemia.

ABSTRACT: The transcription factors PAX5, IKZF1, and EBF1 are frequently mutated in B cell acute lymphoblastic leukemia (B-ALL). We demonstrate that compound heterozygous loss of multiple genes critical for B and T cell development drives transformation, including Pax5^+/-xEbf1^+/-, Pax5^+/-xIkzf1^+/-, and Ebf1^+/-xIkzf1^+/- mice for B-ALL, or Tcf7^+/-xIkzf1^+/- mice for T-ALL. To identify genetic defects that cooperate with Pax5 and Ebf1 compound heterozygosity to initiate leukemia, we performed a Sleeping Beauty (SB) transposon screen that identified cooperating partners including gain-of-function mutations in Stat5b (~65%) and Jak1 (~68%), or loss-of-function mutations in Cblb (61%) and Myb (32%). These findings under

SUBMITTER: Heltemes-Harris LM 

PROVIDER: S-EPMC8556320 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature