KDM6A, a novel prognosis-predictive marker of pediatric acute myeloid leukemia?

Abstract

Background and Aim - Despite advancements in diagnostic techniques and the discovery of newer chemotherapeutic agents, the outcome of acute myeloid leukaemia (AML) remains dismal. H3K27me3 demethylase (KDM6a) is a novel gene with a suggestive role as a tumour suppressor, and loss of KDM6a expression in AML relapse has been previously linked to drug resistance in the adult population leading to poor prognosis. This study is aimed to investigate the role of KDM6a in pediatric AML. Method - This prospective study was carried out from July 2021 to January 2024, where bone marrow aspirate or peripheral blood was taken from children (age ≤18) at diagnosis, remission (at first reported remission either PI-1 or PI-2) and relapse. The extracted RNA was converted to cDNA for expression analysis of KDM6a. The expression dynamics of KDM6a were analysed using qRT-PCR. Results - A total of 74 patients with AML were enrolled in the study after the exclusion of 14 children due to exclusion criteria or low TLC. The most common symptoms observed were fever (78.8%), pallor (54.7%), fatigue (36.7%), and loss of appetite (45.5%). The most common cell surface markers detected were CD33 (100%), CD38 (91.67%), CD117 (87.80%), and CD13 (75%). The expression was downregulated at the diagnosis stage (N=74) compared to the control population (p=<0.0001) (N=10). KDM6a was upregulated at remission compared to diagnosis (p=0.0034) (N=61), whereas its expression decreased on relapse of the disease in paired samples in comparison to remission (p=<0.0001) (N=8). Conclusions - The differential expression of KDM6a exclusively at the diagnosis and relapse stage indicates its role in the pathogenesis of pediatric AML. A study with deeper molecular analysis is required to understand the contribution of KDM6a in cellular changes leading to AML. Given the poor prognosis associated with AML, it is crucial to incorporate new disease markers for better risk assessment and to identify potential therapeutic targets.