Purpose of review: The protein tyrosine phosphatase Shp2 is encoded by PTPN11 and positively regulates physiologic hematopoiesis. Mutations of PTPN11 cause the congenital disorder Noonan syndrome and pathologically promote human leukemias. Given the high frequency of PTPN11 mutations in human disease, several animal models have been generated to investigate Shp2 in hematopoietic stem cell (HSC) function and leukemic transformation. Recent findings: Two independent animal models bearing knockout of Shp2 in hematopoietic tissues clearly demonstrate the necessity of Shp2 in HSC repopulating capacity. Reduced HSC quiescence and increased apoptosis accounts for diminished HSC function in the absence of Shp2. The germline mutation Shp2D61G enhances HSC activity and induces myeloproliferative disease (MPD) in vivo by HSC transformation. The somatic mutation Shp2D61Y produces MPD in vivo but fails to induce acute leukemia, whereas somatic Shp2E76K produces MPD in vivo that transforms into full-blown leukemia. HSCs expressing Shp2D61Y do not generate MPD in recipient animals upon transplantation, whereas Shp2E76K-expressing HSCs yield MPD as well as acute leukemia in recipient animals. The mechanisms underlying the unique functions of Shp2D61Y and Shp2E76K in HSC transformation and leukemogenesis continue to be under investigation. Summary: Further understanding of the physiologic and pathologic role of Shp2 in hematopoiesis and leukemogenesis, respectively, will yield information needed to develop therapeutic strategies targeted to Shp2 in human disease.
- hematopoietic stem cell
ASJC Scopus subject areas
Shp2 function in hematopoietic stem cell biology and leukemogenesis. / Nabinger, Sarah C.; Chan, Rebecca.In: Current Opinion in Hematology, Vol. 19, No. 4, 07.2012, p. 273-279.
Research output: Contribution to journal › Article
TY - JOUR
T1 - Shp2 function in hematopoietic stem cell biology and leukemogenesis
AU - Nabinger, Sarah C.
AU - Chan, Rebecca
PY - 2012/7
Y1 - 2012/7
N2 - Lippincott Williams & Wilkins.
AB - Lippincott Williams & Wilkins.
KW - hematopoietic stem cell
KW - leukemogenesis
KW - PTPN11
KW - Shp2
UR - http://www.scopus.com/inward/record.url?scp=84862137725&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862137725&partnerID=8YFLogxK
U2 - 10.1097/MOH.0b013e328353c6bf
DO - 10.1097/MOH.0b013e328353c6bf
M3 - Article
VL - 19
SP - 273
EP - 279
JO - Current Opinion in Hematology
JF - Current Opinion in Hematology
SN - 1065-6251
IS - 4