Characterization of Acute Myeloid Leukemia with PTPN11 Mutation - The Mutation Is Closely Associated with NPM1 Mutation but Inversely Related to FLT3/ITD.

The development of acute myeloid leukemia (AML) is a multistep process. Recently, somatic mutations of PTPN11, the gene encoding non-receptor protein tyrosine phosphatase SHP-2, were observed in some hematological malignancies. However, the characteristics of adult AML with PTPN11 mutations have not been comprehensively studied, and the specific genetic alteration cooperative with a PTPN11 mutation in the leukemogenesis remains largely unknown. In this study, PTPN11 mutation and its association with other gene aberrations were analysed for 272 adult patients with de novo AML. Missense mutations were identified in 14 individuals (5.1%). The PTPN11 mutation was closely associated with old age (P=0.036), FAB M4/M5 subtypes (P=0.049), CD14 expression (P=0.026), a normal karyotype (P=0.044) and NPM1 mutation (P=0.037), but negatively associated with FLT3/ITD (P = 0.025). In addition, four patients revealed simultaneous mutations of PTPN11 and AML1 (n=3) or MLL (n=1). We observed a shorter overall survival for patients with PTPN11 mutation than those without amongst NPM1-wild patients (P=0.001), but not amongst NPM1-mutated patients (P=0.738). Our findings provide evidence that AML patients with PTPN11 mutations had some distinct biological and clinical characteristics, and the mutation may cooperate with other gene alterations to lead to AML in a subset of patients.