Aim

This study explores the prognostic impact of FLT3-ITD, NPM1, and WT1 mutations both independently and in combination in Cytogenetically Normal Acute Myeloid Leukemia (CN-AML) patients as they exhibit varying clinical outcomes.

Methods

150 CN-AML patients were selected to assess the prevalence and prognostic significance of WT1 mutations in combination with FLT3-ITD and NPM1 status using polymerase chain reaction (PCR) followed by Sanger sequencing.

Results

WT1 exon 7 mutations were present in 12.6% of patients. Elderly individuals, with a mean age of 49.4 years, were more prone to NPM1 mutations, though the association was not statistically significant (p=0.094). Significant associations were observed between lactate dehydrogenase (LDH) and hemoglobin (Hb) levels with FLT3-ITD and NPM1 mutations (p=0.003 and p=0.04, respectively). The M4 subtype exhibited the highest prevalence of WT1 mutations (p=0.0036). Patients with NPM1 mutations had a higher overall survival rate compared to NPM1 wild-type cases (p=0.057). There was no significant correlation between overall survival and WT1 and FLT3-ITD mutations. Regarding relapse-free survival, NPM1 mutation cases exhibited a higher survival probability compared to NPM1 wild-type cases. Similarly, WT1 mutated cases had a higher survival probability compared to WT1 wild-type cases, although these differences were not statistically significant. The combined mutation statuses of NPM1/FLT3-ITD with WT1 did not yield significant outcomes. The study suggests that larger cohort studies may reveal more relevant associations, given the relatively small cohort in this study.

Conclusion

This study found a significant association between patient survival outcomes and NPM1 mutation status, as well as the combined FLT3-ITD and NPM1 status. Profiling both NPM1 and FLT3-ITD mutations at the time of diagnosis serves as a robust prognostic marker in AML treatment. WT1 mutation status did not show a significant association with patient outcomes. Larger population studies may provide more relevant insights.