Pattern and prognostic value of FLT3‐ITD mutations in Chinese de novo adult acute myeloid leukemia

摘要

FMS‐like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in hematological malignancies. FLT3 internal tandem duplication (FLT3‐ITD) mutations located in juxtamembrane domain (JMD) and tyrosine kinase domain 1 (TKD1) regions account for two‐thirds of all FLT3 mutations. The outcome of patients remains unsatisfactory, with low survival rates. It is not yet known whether the different mutations within the FLT3 gene are all associated with patient outcome. In addition, the cause of FLT3‐ITD in‐frame duplication events remains unknown. Although there are some published studies investigating the FLT3‐ITD mutation and its clinical implications in Chinese acute myeloid leukemia (AML) patients, sample sizes tend to be small and detailed molecular profiles of FLT3 mutations are lacking in these studies. In our study, 227 FLT3‐ style="fixed-case">ITD sequences were analyzed from 227 Chinese de novo style="fixed-case">AML patients. style="fixed-case">ITD were next classified into 3 types based on molecular profiles of insertion style="fixed-case">DNA sequences: style="fixed-case">DNA complete duplication (type I), style="fixed-case">DNA partial duplication (type style="fixed-case">II) and complete random sequence (type style="fixed-case">III). From the 154 patients, we confirmed that high style="fixed-case">ITD allelic ratio (≥.5) and allogeneic stem cell transplant treatment under style="fixed-case">CR1 are independent prognostic factors. We also presented evidence that style="fixed-case">ITD integration sites in the hinge region or beta1‐sheet region are an unfavorable prognostic factor in adult style="fixed-case">AML patients with style="fixed-case">FLT3‐ style="fixed-case">ITD mutations. These findings may help to decipher the mechanisms of style="fixed-case">FLT3‐ style="fixed-case">ITD in‐frame duplication events and stratify patients when considering different therapeutic combinations.