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

Hanan M Bedair,Fatma M Khalaf,Hatem Rabie,Mohamed H Attia,Sahar Badr El-Din,Suzy F Gohar

doi:10.1186/s43042-021-00183-8

Abstract

BackgroundThere 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.ResultsSixty-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).ConclusionMutant WT1 genotypes (SNP rs16754) were conversely, associated with complete response, and hMICL overexpression had poor prognostic value in AML.

Highlights

There are several genetic mutations that carry prognostic and predictive values in acute myeloid leukemia (AML)
Genotyping of Wilms’ tumor-1 (WT1) showed that the AA was the most prevalent genotype and present in 46 (73%) patients with AML, followed by at the heterozygous state (AG) genotype in 15 (23.8%) patients, while the least prevalent genotype is the GG genotype, which was noted in 2 patients (3.2%) (Table 2)
The current study investigated the relationship between WT1 genotypes and the promising marker human myeloid inhibitory C-type lectin-like (hMICL) receptor expression in 63 patients with Cytogenetically normal AML (CN-AML) and determined the treatment outcome in these patients

Summary

Introduction

There are several genetic mutations that carry prognostic and predictive values in acute myeloid leukemia (AML). They are implicated in disease pathogenesis and patient outcome. 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. Many curatively treated patients with AML have relapse but estimated to be in complete remission (CR) by standard diagnostic criteria [2] This is thought to be caused by the presence and outgrowth of sustaining leukemic stem cells in the bone marrow (BM), termed minimal residual disease (MRD) [3]. Formal proof supporting preventive intervention of patients with MRD-positive AML is still limited [6, 7]

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