Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0002874 (
aplastic anemia
)
5,905
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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
KIT
D816V
induction prevented expansion of red blood cells, but rapidly lead to a state of
aplastic anemia
and bone marrow fibrosis, reminiscent of post polycythemic myeloid metaplasia, the spent phase of polycythemia vera. Our results show that the extramedullary hematopoietic niche microenvironment significantly influences disease outcome in
KIT
D816V
mutant mice, turning this model a valuable tool for studying the interplay between functionally abnormal hematopoietic cells and their microenvironment during development of polycythemia vera-like disease and myelofibrosis.
...
PMID:The spleen microenvironment influences disease transformation in a mouse model of KIT
D816V
-dependent myeloproliferative neoplasm. 2812 88
