Pediatric mastocytosis-associated KIT extracellular domain mutations exhibit different functional and signaling properties compared with KITphosphotransferase domain mutations.

ABSTRACT: Most adult patients have a D816V mutation in phosphotransferase domain (PTD), we have described that half of the children carry mutations in extracellular domain (ECD). KIT-ECD versus IT-PTD-mutants were introduced into rodent Ba/F3, EML, Rat2 and human TF1 cells to investigate their biological effect. ECD- and PTD-mutants also displayed distinct whole-genome transcriptional profiles in EML cells. We observed differences in their signaling properties: they both activated STAT pathways, whereas AKT pathway was only activated by ECD-mutants. Consistently, AKT inhibitor suppressed ECD-mutant-dependent proliferation, clonogenicity and erythroid differentiation. Expression of myristoylated AKT restored erythroid differentiation in EMLPTD cells, suggesting the differential role of AKT in those m

ORGANISM(S): Mus musculus

SUBMITTER: Pascal FINETTI 

PROVIDER: E-GEOD-21255 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress