P576: Prevalence and Clinical Significance of Germline Mutations in Acute Myeloid Leukemia Patients - a Single-center Experience
Year: 2023
Type: conference-abstract
Study design: Observational Study
Abstract: Background: Acute myeloid leukemia (AML) is a heterogeneous disease with complex genetic landscape. Germline mutations have been identified in several AML patients and may have important implications for treatment and outcome. The recognition of germline predisposition to hematological cancers is becoming more prevalent. The increased use of high-throughput and whole genome sequencing is identifying a significant number of underlying germline mutations that cause such cancers. Aims: This study aimed to investigate the prevalence and clinical significance of germline mutations in a cohort of AML patients. Methods: We conducted a retrospective analysis of 51 AML patients who had been diagnosed and treated at the East Suffolk and North Essex foundation NHS trust. Patients were included in the study if they had a germline mutation in one of five genes: GATA2, DDX41, RUNX1, ETV6, or CEBPA. We collected clinical and genomic data for each patient, including their date of birth, date of diagnosis, germline mutation, other mutations, FISH status, karyotype status, ELN risk stratification category, date of last treatment, and date of death/still alive status. Results: Of the 51 patients, 13 had a germline mutation in one of the five genes of interest. The prevalence of germline mutations in our cohort was 25.5%. The most commonly identified mutations were CEBPA (30.8%) and RUNX1 (53.8%), with none of the patients being positive for GATA2. Most of the patients (12 out of 13) had additional somatic mutations and karyotype abnormalities, with varying degrees of complexity. Karyotype abnormalities, including trisomy 8 and translocations between chromosome 12 and chromosome 22, were observed in some patients. The 2022 ELN risk stratification category was adverse in 6 patients, intermediate in 6 patients, and favorable in 1 patient. Patients with germline mutations had a range of overall survival (OS) and progression-free survival (PFS) times, with some patients still alive at the time of data analysis. Summary/Conclusion: Our study highlights the prevalence of germline mutations in a significant proportion of AML patients, and these mutations may have important implications for diagnosis, risk stratification, and treatment. Although the ELN risk stratification was available for all patients, we acknowledge that there are other factors affecting clinical outcome, and further research is needed to validate our findings and to determine the optimal management strategies for AML patients with germline mutations. Further research is needed to better understand the role of germline mutations in AML and to develop more personalized approaches to treatment and management. Keywords: Genomics, Mutation status, Mutation analysis, Acute myeloid leukemia
Source: HemaSphere
Authors: Sheraz Bashir, Victor Ling, Chrishthuka Kangatharan, Michelle Richardson, Seoksan Teh, Zafar Ullah, Nicola Gill, Jayne Chappells, Joanne King, Ioana Nitu-Whalley, Debo Ademokun, Andrew Hodson, Mahesh Prahladan
Institution: East Suffolk and North Essex NHS Foundation Trust
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,480
OpenAlex ID: W4386024751