Spred1 deficit promotes treatment resistance and transformation of chronic phase CML.

ABSTRACT: Spred1 is highly expressed in normal hematopoietic stem cells (HSCs). Lack of Spred1 function has been associated with aberrant hematopoiesis and acute leukemias. In chronic myelogenous leukemia (CML), Spred1 is reduced in patients with accelerated phase (AP) or blast crisis (BC) CML, thereby suggesting that deficit of this protein may contribute to disease transformation. In fact, Spred1 knockout (KO) in SCLtTA/BCR-ABL CML mice either globally, or restricted to hematopoietic cells (i.e., HSCs) or to endothelial cells (ECs), led to transformation of chronic phase (CP) CML into AP/BC CML. Upon BCR-ABL induction, all three Spred1 KO CML models showed AP/BC features. However, compared with global Spred1 KO, the AP/BC phenotypes of HSC-Spred1 KO and EC-Spred1 KO CML models were attenuated, sug

SUBMITTER: Qiao J 

PROVIDER: S-EPMC9134843 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature