Prevalence of RUNX1 gene alterations in de novo adult acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a complicated disease with uncontrolled hematopoietic precursor proliferation induced by various genetic alterations. Runt-related transcription factor-1 (RUNX1) is commonly disrupted by chromosomal translocations in hematological malignancies.

Aim: To characterize RUNX1 gene rearrangements and copy number variations in newly diagnosed adult AML patients, with an emphasis on the impact of clinical and laboratory features on the outcome.

Methods: Fluorescence in situ hybridization was used to test RUNX1 gene alterations in 77 newly diagnosed adult AML cases. NPM1, FLT3/ITD, FLT3/TKD, and KIT mutations were tested by PCR. Prognostic clinical and laboratory findings were studied in relation to RUNX1 alterations.

Results: RUNX1 abnormalities were detected by fluorescence in situ hybridization in 41.6% of patients: 20.8% had translocations, 22.1% had amplification, and 5.2% had deletion. Translocations prevailed in AML-M2 (P = 0.019) with a positive expression of myeloperoxidase (P = 0.031), whereas deletions dominated in M4 and M5 subtypes (P = 0.008) with a positive association with CD64 expression (P = 0.05). The modal chromosomal number was higher in cases having amplifications (P = 0.007) and lower in those with deletions (P = 0.008). RUNX1 abnormalities were associated with complex karyotypes (P < 0.001) and were mutually exclusive of NPM1 mutations. After 44 months of follow-up, RUNX1 abnormalities affected neither patients' response to treatment nor overall survival.

Conclusion: RUNX1 abnormalities were mutually exclusive of NPM1 mutations. RUNX1 abnormalities affected neither patients' response to treatment nor overall survival.