The spleen microenvironment influences disease transformation in a mouse model of KIT^D816V-dependent myeloproliferative neoplasm.

ABSTRACT: Activating mutations leading to ligand-independent signaling of the stem cell factor receptor KIT are associated with several hematopoietic malignancies. One of the most common alterations is the D816V mutation. In this study, we characterized mice, which conditionally express the humanized KIT^D816V receptor in the adult hematopoietic system to determine the pathological consequences of unrestrained KIT signaling during blood cell development. We found that KIT^D816V mutant animals acquired a myeloproliferative neoplasm similar to polycythemia vera, marked by a massive increase in red blood cells and severe splenomegaly caused by excessive extramedullary erythropoiesis. Moreover, we found mobilization of stem cells from bone marrow to the spleen. Splenectomy prior to K

SUBMITTER: Pelusi N 

PROVIDER: S-EPMC5269732 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature