The prognostic impact of Wilms tumor-1 polymorphism (rs16754) and human myeloid inhibitory C-type lectin-like receptor expression in cytogenetically normal-acute myeloid leukemia

Abstract

Abstract Background There are several genetic mutations that carry prognostic and predictive values in acute myeloid leukemia (AML). They are also implicated in disease pathogenesis and patient outcome. They can be a target of novel therapies for AML. The aim of the current study was to investigate prognostic value of Wilms’ tumor-1 (WT1) genotypes and human myeloid inhibitory C-type lectin-like (hMICL) receptor expression in normal-cytogenetic group of patients with AML. Genotyping of WT1 mutations was done by Rotor Gene real-time polymerase chain reaction (PCR) while hMICL expression was detected using phycoerythrin (PE)-conjugated mouse monoclonal anti-human (MoAbs) by flow cytometry. Results Sixty-three patients with cytogenetically normal AML (CN-AML) were included in the study. The alternate allele of WT1 single nucleotide polymorphism (SNP) rs16754 was found in 26.89%. At day 28 of therapy, complete remission was achieved in 100% of cases harboring mutant AG plus GG genotypes but only in 6.38% of cases harboring wild genotype (AA). After 6 months, 88.23% of patients harboring WT1 mutant genotype maintained complete remission, while only 23.40% of patients with wild type showed complete remission. The overall survival in patients harboring mutant WT1 genotypes was significantly longer than in those who carried the wild type gene (P-value, 0.001). Additionally, hMICL was overexpressed in approximately 87.3% of AML cases and inversely related to complete response. Similarly, overall survival was significantly shorter in patients with positive hMICL (P-value, 0.001). Conclusion Mutant WT1 genotypes (SNP rs16754) were conversely, associated with complete response, and hMICL overexpression had poor prognostic value in AML.

Keywords

• Acute leukemia
• Myeloid neoplasm
• Cytogenetic
• Genotypes
• Prognosis
• Wilms’ tumor