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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
HLF gene is a poor prognostic factor in acute myeloid leukemia patients with FLT3-ITD/NPM1 mutations undergoing
Xiaoyu Xu1, Xinxin Ge1, Airui Jiang1
1Jiangsu Institute of Hematology, National Center of Hematological Clinical Medicine Research, NHC Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, the First Affiliated Hospital of Soochow University, Suzhou, China.
Acute myeloid leukemia (AML) patients with FLT3-ITD mutations were benefit from hematopoietic cell transplantation (HSCT) in the first complete remission. Previous research suggested that newly diagnosed AML patients with high allelic ratio (AR) of FLT3-ITD have unfavorable survivals, while newly diagnosed AML patients with lower FLT3-ITD AR and concomitant NPM1 mutations have favorable outcomes. In AML patients with FLT3-ITD, co-occurrence with DNMT3A, and NPM1 mutations (triple-mutated AML patients) have the worst prognoses, however, it is little known about how these mutations synergize in these triple-mutated AML patients. Here we showed that hepatic leukemia factor (HLF) gene was more highly expressed in triple-mutated AML patients than in those without the DNMT3A mutations. We found that HLF gene expressions had significant difference in triple-mutated and FLT3-ITD/NPM1 AML patients (double-mutated AML patients). Moreover, in DNMT3A mutated AML patients, correlated with high HLF gene expression, which may be itself associated with poor survival rate and drug resistance. Overall our data establish that HLF gene as a novel biomarker in this genetically defined the triple-mutated AML subgroup.
Acute myeloid leukemia (AML) patients with FLT3-ITD mutations were benefit from hematopoietic cell transplantation (HSCT) in the first complete remission. Previous research suggested that newly diagnosed AML patients with high allelic ratio (AR) of FLT3-ITD have unfavorable survivals, while newly diagnosed AML patients with lower FLT3-ITD AR and concomitant NPM1 mutations have favorable outcomes. In AML patients with FLT3-ITD, co-occurrence with DNMT3A, and NPM1 mutations (triple-mutated AML patients) have the worst prognoses, however, it is little known about how these mutations synergize in these triple-mutated AML patients. Here we showed that hepatic leukemia factor (HLF) gene was more highly expressed in triple-mutated AML patients than in those without the DNMT3A mutations. We found that HLF gene expressions had significant difference in triple-mutated and FLT3-ITD/NPM1 AML patients (double-mutated AML patients). Moreover, in DNMT3A mutated AML patients, correlated with high HLF gene expression, which may be itself associated with poor survival rate and drug resistance. Overall our data establish that HLF gene as a novel biomarker in this genetically defined the triple-mutated AML subgroup.

