Implications of Incorporating Myelodysplasia-Related Gene Variant Data on Acute Myeloid Leukemia Reclassification...

In the 5th edition of the WHO Classification of Hematopoietic Neoplasms (WHO-HAEM5) and the International Consensus Classification (ICC), acute myeloid leukemia (AML) diagnostic criteria were revised to incorporate genetic abnormalities, such as variants in myelodysplasia-related (MR) genes. As the implications of these changes on AML reclassification in Korean patients had not yet been fully evaluated, we comprehensively investigated them in this large-scale, multicenter study.

We retrospectively analyzed data from 2,668 patients with AML aged ≥ 18 yrs from seven institutions who were originally diagnosed according to WHO-HAEM4R criteria. Clinical, cytogenetic, and targeted next-generation sequencing data (including MR genes and TP53 variants) were collected and analyzed. All cases were reassessed according to both WHO-HAEM5 and ICC criteria.

Overall, 28.5% of patients harbored at least one MR gene variant. Among the MR genes, variants in RUNX1 and ASXL1 were most frequently detected. Compared with the original diagnoses, 20.3% and 29.9% of patients were reclassified to different categories according to the WHO-HAEM5 and ICC criteria, respectively. Discordance between WHO-HAEM5 and ICC classifications was 13.2%, which is largely attributed to the inclusion of "AMLs with TP53" variants in the ICC. AML-MR was associated with older age, male predominance, and poorer survival compared with AML, not otherwise specified. Patients with recurrent fusion genes largely retained their original classification.

Incorporating MR gene variant data and TP53-variant status in diagnosis influenced AML classification and risk stratification in our cohort, highlighting the potential importance of comprehensive molecular profiling in AML characterization.