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.