Assessment of fragile histidine triad (FHIT) gene expression as a predictive biomarker of therapeutic response in chronic myeloid leukemia

Abstract: BACKGROUND: The accumulation of other abnormalities in both genetic and epigenetic pathways, in addition to the BCR-ABL1 oncoprotein, affects the overall clinical consequences of chronic myeloid leukemia (CML), including treatment responsiveness. OBJECTIVES: This study investigated the expression levels of fragile histidine triad ( FHIT ) gene among patients with CML and evaluated its association with the response of patients to imatinib mesylate treatment. PATIENTS AND METHODS: Samples of blood were provided from sixty CML patients: Thirty responsive and thirty nonresponsive patients to imatinib mesylate treatment, as well as sixty healthy controls matched for age and sex were provided blood samples. The FHIT gene expression was estimated using reverse transcription quantitative polymerase chain reaction. RESULTS: The results indicated that FHIT gene expression was significantly lower in CML patients than in the controls ( P < 0.001). Compared to the responsive CML patients, the nonresponsive CML patients presented a significantly decreased level of FHIT gene expression ( P < 0.001). A significant increase in FHIT gene expression was found at a cut-off value of more than 0.0578 for distinguishing responsive from nonresponsive CML patients, as shown by receiver operating characteristic analysis, with 97% sensitivity and 72.4% specificity. CONCLUSIONS: Reduced FHIT gene expression was associated with CML and with changes in hematopoietic patterns observed in the studied patients. Variations in FHIT expression were noted between responsive and nonresponsive patients, indicating a potential association with treatment response, suggesting that FHIT expression may have value as a complementary predictive biomarker for imatinib mesylate responsiveness, although further validation is required.