GAB2, a scaffolding adaptor that binds and activates SHP2, is essential for leukemogenesis by BCR-ABL1, and a GAB2 mutant lacking SHP2 binding cannot mediateleukemogenesis.
We identified TET2 and PTPN11 mutations in both mouse and human AML and then demonstrated the ability of Tet2 loss and PTPN11D61Y to initiate leukemogenesis in concert with expression of AML1-ETO in vivo.
Against original prediction as tumor suppressor for tyrosine phosphatases, PTPN11 was first identified as a proto-oncogene because activating mutations of this gene are associated with leukemogenesis.
Somatic PTPN11 mutations contribute to leukemogenesis in children with hematologic malignancies including juvenile myelomonocytic leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, and myelodysplasia.
Mutations of the protein tyrosine phosphatase SHP-2 are implicated in human diseases, causing Noonan syndrome (NS) and related developmental disorders or contributing to leukemogenesis depending on the specific amino acid substitution involved.
These data suggest that PTPN11 mutation may play an important role for leukemogenesis in a proportion of children with ALL, particularly B precursor ALL.
Germline mutations in PTPN11, the gene encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome (NS) and the clinically related LEOPARD syndrome (LS), whereas somatic mutations in the same gene contribute to leukemogenesis.
Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia.
To test the hypothesis that PTPN11 mutations might contribute to myeloid leukemogenesis, we screened the entire coding region for mutations in 51 JMML specimens and in selected exons from 60 patients with other myeloid malignancies.
This review focuses on the non-receptor Src-homology 2 domain-containing protein tyrosine phosphatase SHP-2 and its role in signal transduction, hematopoiesis, and leukemogenesis.