Loss of Pax5 Exploits Sca1-BCR-ABL^p190 Susceptibility to Confer the Metabolic Shift Essential for pB-ALL.

ABSTRACT: Preleukemic clones carrying BCR-ABL^p190 oncogenic lesions are found in neonatal cord blood, where the majority of preleukemic carriers do not convert into precursor B-cell acute lymphoblastic leukemia (pB-ALL). However, the critical question of how these preleukemic cells transform into pB-ALL remains undefined. Here, we model a BCR-ABL^p190 preleukemic state and show that limiting BCR-ABL^p190 expression to hematopoietic stem/progenitor cells (HS/PC) in mice (Sca1-BCR-ABL^p190) causes pB-ALL at low penetrance, which resembles the human disease. pB-ALL blast cells were BCR-ABL-negative and transcriptionally similar to pro-B/pre-B cells, suggesting disease onset upon reduced Pax5 functionality. Consistent with this, double Sca1-BCR-ABL<

SUBMITTER: Martin-Lorenzo A 

PROVIDER: S-EPMC6245574 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature