Distinct and targetable role of calcium-sensing receptor in leukaemia.

ABSTRACT: Haematopoietic stem cells (HSC) reside in the bone marrow microenvironment (BMM), where they respond to extracellular calcium [eCa²⁺] via the G-protein coupled calcium-sensing receptor (CaSR). Here we show that a calcium gradient exists in this BMM, and that [eCa²⁺] and response to [eCa²⁺] differ between leukaemias. CaSR influences the location of MLL-AF9⁺ acute myeloid leukaemia (AML) cells within this niche and differentially impacts MLL-AF9⁺ AML versus BCR-ABL1⁺ leukaemias. Deficiency of CaSR reduces AML leukaemic stem cells (LSC) 6.5-fold. CaSR interacts with filamin A, a crosslinker of actin filaments, affects stemness-associated factors and modulates pERK, β-catenin and c-MYC signaling and intracellular levels of [Ca

SUBMITTER: Pereira RS 

PROVIDER: S-EPMC10558580 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature