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. 2024 Oct 1;25(10):3463-3470.
doi: 10.31557/APJCP.2024.25.10.3463.

Exploring the Prevalence and Prognostic Impact of Wilms Tumor 1 Exon 7 Mutation Status with Combinations of FLT3-ITD and NPM1 Mutations as Potential Molecular Biomarkers in Acute Myeloid Leukemia Patients with Normal Cytogenetics

Geetha Raj John Anitha  1 , Vineetha Radhakrishnan Chandraprabha  1 , Devipriya Padmakumar  1 , Mahitha Mohanan Sreelatha  1 , Amritha Padmakumar  1 , Preethi Gopinath  1 , Akhila Raj Thampirajan Vimala Devi  1 , Suraj Lathika Surendran  2 , Geetha Narayanan  3 , Hariharan Sreedharan  2 , Jagathnath Krishna Kumarapillai Mohanan Nair  4
Affiliations

Exploring the Prevalence and Prognostic Impact of Wilms Tumor 1 Exon 7 Mutation Status with Combinations of FLT3-ITD and NPM1 Mutations as Potential Molecular Biomarkers in Acute Myeloid Leukemia Patients with Normal Cytogenetics

Geetha Raj John Anitha et al. Asian Pac J Cancer Prev. .

Abstract

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.

Keywords: CN AML; FLT3 ITD; NPM1; Prognosis; WT1 Mutation.

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Figures

Figure 1
Figure 1
Mutations and Polymorphic Variants Identified in WT1 Exon 7, Polymorphic Variant(A)- c.1122A˃G, CGA˃CGG, p.Arg374Arg (rs17654),Mutant(B)- c.1148-1157dupTTGTACGGTC
Figure 2
Figure 2
Kaplan–Meier Survival Estimates for OS (24 months) of FLT3-ITD(A), NPM1(B), and WT1(C).
Figure 3
Figure 3
Kaplan–Meier Survival Estimates for RFS (24 months) of FLT3-ITD(A), NPM1(B), and WT1(C).
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