Focal Adhesion Genes Refine the Intermediate-Risk Cytogenetic Classification of Acute Myeloid Leukemia

Abstract

In recent years, several attempts have been made to identify novel prognostic markers in patients with intermediate-risk acute myeloid leukemia (IR-AML), to implement risk-adapted strategies. The non-receptor tyrosine kinases are proteins involved in regulation of cell growth, adhesion, migration and apoptosis. They associate with metastatic dissemination in solid tumors and poor prognosis. However, their role in haematological malignancies has been scarcely studied. We hypothesized that PTK2/FAK, PTK2B/PYK2, LYN or SRC could be new prognostic markers in IR-AML. We assessed PTK2, PTK2B, LYN and SRC gene expression in a cohort of 324 patients, adults up to the age of 70, classified in the IR-AML cytogenetic group. Univariate and multivariate analyses showed that PTK2B, LYN and PTK2 gene expression are independent prognostic factors in IR-AML patients. PTK2B and LYN identify a patient subgroup with good prognosis within the cohort with non-favorable FLT3/NPM1 combined mutations. In contrast, PTK2 identifies a patient subgroup with poor prognosis within the worst prognosis cohort who display non-favorable FLT3/NPM1 combined mutations and underexpression of PTK2B or LYN. The combined use of these markers can refine the highly heterogeneous intermediate-risk subgroup of AML patients, and allow the development of risk-adapted post-remission chemotherapy protocols to improve their response to treatment.