NEXT-GENERATION-SEQUENCE-BASED GENE MUTATION DETECTION AND ITS CLINICAL SIGNIFICANCE IN PATIENTS WITH ACUTE MYELOID LEUKEMIA.
Author(s): ,
Jifeng Yu
Affiliations:
Department of Hematology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,China
,
Tao Li
Affiliations:
Department of Hematology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,China
,
Yafei Li
Affiliations:
Department of Hematology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,China
,
Yingmei Li
Affiliations:
Department of Hematology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,China
,
Haizhou Xing
Affiliations:
Department of Hematology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,China
,
Hui Sun
Affiliations:
Department of Hematology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,China
,
Dingming Wan
Affiliations:
Department of Hematology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,China
,
Yanfang Liu
Affiliations:
Department of Hematology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,China
,
Chong Wang
Affiliations:
Department of Hematology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,China
,
Xinsheng Xie
Affiliations:
Department of Hematology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,China
Zhongxing Jiang
Affiliations:
Department of Hematology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,China
EHA Library. Yu J. Jun 14, 2019; 266047; PF249
Jifeng Yu
Jifeng Yu
Contributions
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Abstract

Abstract: PF249

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background
     Acute myeloid leukemia (AML) is a biologically heterogeneous disease with many different cytogenetic disorders and gene mutations. The advances of the next-generation sequence (NGS) made it more practical for the clinical research to explore the cytogenetic analysis and mutation testing for the classification and risk assessment of AML patients.

Aims
     In this study, we sought to investigate the differences in molecular gene mutations between different type of AML patients and the response from those newly diagnosed AML patients to induction chemotherapy.

Methods
     We retrospectively evaluated 274 hospitalized non-M3 AML patients. A next-generation sequencing assay covering 43 genes was used to investigate recurrently mutated genes. The mutational status of fusion genes was determined by real time PCR. Clinical follow up was based on the patients recent clinic visits. Correlation analysis was done based different groups classified by different categories.

Results
     The median age at diagnosis was 45 year-old (range 16-81 years). 231 patients were 59 years or younger with the median age of 41 years. Forty-three patients were 60 years or older with a median age of 69 years (range 60-81 years). At least one non-synonymous gene mutation was detected in 233 patients (85%). The median number of gene mutations was two (range 0-8). Comparing to the 59 years or younger patients, there was a significantly higher incidence of gene mutation in 60 years and older patients (p <0.01).  The mean number of molecular gene mutations at diagnosis was higher in older patients than younger patients (2.92 vs 1.48, p<0.05). Older patients had significantly higher frequency of ASXL1 (23.3% vs 13.9%, p <0.05), TP53 (11.6% vs 1.7%, p <0.05), IDH2 (18.6% vs 4.3%, p<0.05) mutations, higher frequency of CEBPA (21.2% vs 14%, p<0.05).  Among 11 patients with no gene mutation received DA (daunorubicin 80 mg/m2 per day on days 1-3 and cytarabine 100 mg/m2 twice per day on days 1-7) as the induction therapy, 8 patients (73%) achieved CR after 1 course induction treatment. Meanwhile, among 21 patients with one or more gene mutations received DA induction therapy, only 12 patients (57%) achieved CR after 1 course induction treatment. More data need to be collected regarding the significance of each individual gene fusion correlating with induction chemotherapy.

Conclusion
     A higher incidence of cytogenetic disorders was found in older AML patients with  higher burdens of molecular mutations, comparing to younger patients.  Also, significantly higher frequency of ASXL1, TP53, IDH2 and CEBPA had been found with older patients. Patients with fewer gene fusion had a better chance of achieving CR when treated with cytarabine and daunorubicin induction chemotherapy.

Session topic: 3. Acute myeloid leukemia - Biology & Translational Research

Keyword(s): Acute myeloid leukemia, Gene expression, Induction chemotherapy

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