Oncogenic FLT3 internal tandem duplications (ITD) and CD45/PTPRC control osteoclast functions and bone microarchitecture.

ABSTRACT: Activating internal tandem duplications (ITD) in the juxtamembrane domain of receptor tyrosine kinase FLT3 occur frequently in patients with acute myeloid leukemia (AML). Constitutive active FLT3-ITD mutations induce aberrant signaling and promote leukemic cell transformation. Inactivation of the attenuating receptor protein tyrosine phosphatase CD45 (PTPRC) in FLT3-ITD mice resulted in the development of a severe hematopoietic phenotype with characteristics of AML. In addition, abnormal bone structures and ectopic bone formation were observed in these mice, suggesting a previously unknown role of FLT3 to control bone development and remodeling. While Ptprc knockout and Flt3-ITD mutant mice showed a largely normal bone microarchitecture, micro-CT analysis of femurs from Flt3-ITD Ptprc knoc

SUBMITTER: Lossius-Cott C 

PROVIDER: S-EPMC11788565 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature