TY - JOUR AU - Wu, Jie PY - 2015 TI - Shp2 regulates leukemic stem cell frequency in MLL-rearranged acute myeloid leukemia JF - Stem Cell Investigation; Vol 2, No 4 (April 2015): Stem Cell Investigation Y2 - 2015 KW - N2 - Shp2 is a non-receptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene. It contains two SH2 domains, a PTP domain, and a carboxyl-terminal region with tyrosine phosphorylation sites. The Shp2 PTP activity is autoinhibited by its N-SH2 domain. Shp2 is activated by docking to specific tyrosine phosphorylated sites via SH2 domains or by gain-of-function (GOF) mutations that disrupt the autoinhibition. GOF Shp2 mutations are most frequently detected in juvenile myelomonocytic leukemia (JMML), representing 35% of cases. Animal model studies using conditional knockin of GOF Shp2 E76K or Shp2 D61G in the hematopoietic compartments have shown that these Shp2 mutants cause JMML-like myeloproliferative disease (MPD), albeit after ~6 months of latency (1,2). UR - https://sci.amegroups.org/article/view/6160