An instructive role for Interleukin-7 receptor α in the development of human B-cell precursor leukemia.

ABSTRACT: Kinase signaling fuels growth of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Yet its role in leukemia initiation is unclear and has not been shown in primary human hematopoietic cells. We previously described activating mutations in interleukin-7 receptor alpha (IL7RA) in poor-prognosis "ph-like" BCP-ALL. Here we show that expression of activated mutant IL7RA in human CD34⁺ hematopoietic stem and progenitor cells induces a preleukemic state in transplanted immunodeficient NOD/LtSz-scid IL2Rγ^null mice, characterized by persistence of self-renewing Pro-B cells with non-productive V(D)J gene rearrangements. Preleukemic CD34⁺CD10^highCD19⁺ cells evolve into BCP-ALL with spontaneously acquired Cyclin Dependent Kinase Inhibitor 2

SUBMITTER: Geron I 

PROVIDER: S-EPMC8814001 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature