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

• Published in: Egyptian Journal of Medical Human Genetics Vol. 22; no. 1; pp. 64 - 12
• Main Authors: Bedair, Hanan M., Attia, Mohamed H., Gohar, Suzy F., Khalaf, Fatma M., Badr El-DIN, Sahar, Rabie, Hatem
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 12.07.2021; Springer; Springer Nature B.V; SpringerOpen
• Subjects: Acute leukemia; Acute myeloid leukemia; Cytogenetic; Cytogenetics; Ethylenediaminetetraacetic acid; Flow cytometry; Gene mutations; Gene polymorphism; Genes; Genetic aspects; Genotypes; Genotyping; Lectins; Leukemia; Medicine; Medicine & Public Health; Mutants; Mutation; Myeloid neoplasm; Polymerase chain reaction; Polymorphism; Prognosis; Remission; Remission (Medicine); Single nucleotide polymorphisms; Single-nucleotide polymorphism; Survival; Tumors; Wilms’ tumor; Egypt; Acute leukemia; Prognosis; Wilms’ tumor; Myeloid neoplasm; Genotypes; Cytogenetic
• ISSN: 1110-8630; 2090-2441
• DOI: 10.1186/s43042-021-00183-8

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.