Prognostic relevance of and mutations in cytogenetically normal adult AML patients.

BACKGROUND

Acute myeloid leukemia with normal cytogenetics (CN-AML) is the largest group of AML patients with very heterogenous patient outcomes. The revised World Health Organization classification of the hematolymphoid tumours, 2022, has incorporated AML with Nucleophosphmin1 () and CCAAT/enhancer binding protein-alpha () mutations as distinct entities. Despite the existing evidence of the prognostic relevance of FMS-like tyrosine kinase-3 internal tandem duplication () in AML, it has not been included in the revised classification.

METHOD

In this prospective study, we determined the prevalence of and gene mutations in 151 de novo CN-AML adult patients (age ≥18 years) in a tertiary care hospital in north India. Additionally, the prognostic relevance of these mutations was also evaluated.

RESULTS

and mutations were found in 33.11%, 23.84%, and 15.77% of CN-AML patients, respectively. mutations were found at 3 domains: transactivation domain 1 (TAD1) in 10 (6.62%), transactivation domain 2 (TAD2) in 5 (3.31%), and basic leucine zipper domain (bZIP) in 11 (7.82%) patients. Patients with mutation had better clinical remission rate (CR) (P=0.003), event-free survival (P=0.0014), and overall survival (OS) (P=0.0017). However, and did not show any association with CR (P=0.404 and 0.92, respectively). Biallelic mutations were found in 12 (7.95%) patients and were associated with better OS (P=0.043).

CONCLUSIONS

These findings indicate that and mutations can be precisely used for risk stratification in CN-AML patients.