91P - Are patients with measurable residual disease (MRD) positive or MRD negative different in baseline DNA methylation signatures in precursor B-cell acute lymphoblastic leukaemia (B-ALL)?

Background

ALL, the most common childhood malignancy is caused by rapid proliferation of blasts. Genetic alterations inherent to blasts are main cause of etiopathogenesis. Relatively little is known about epigenomic alterations, specifically DNA methylation. Aim- To identify regions of aberrant DNA methylation in MRD-positive and MRD-negative Pre-B- ALL patients.

Methods

A total of 12 samples were subjected to deep bioinformatics analysis. We investigated DNA methylomes of 8 newly diagnosed paediatric Pre-B- ALL using Whole-genome Bisulphite sequencing (WGBS). These patients were further categorized based on measurable residual disease (MRD). From a cohort of 142 patients recruited for other study objectives, baseline samples (N=4 +4) were taken for patients who at post-induction exhibited either MRD positivity or MRD negativity as their outcome. For methylation analysis, the WGCNA and differential methylation of promoters techniques were employed. Furthermore, for comparison, DNA samples from healthy individuals(N = 4) were gathered. The following table contains clinical details for the B-ALL patients. Table: 91P

Details of B-ALL patients

Results

Average methylation in terms of density was 75-85% for ALL and 80% for healthy controls. Between MRD-positive and MRD-negative patients, 31,015 Differentially Methylated Regions (DMRs) were found, comprising 18,684 hypermethylated and 12,331 hypomethylated regions. Data from the methylation matrix and patient clinical outcomes were included in the WGCNA analysis. Compared to MRD-positive patients, it was shown that MRD-negative individuals had hypermethylation of EYA4 (linked to cell death), hypomethylation of SLC25A26, and KCNG2 genes.

Conclusions

Pre-B-ALL is characterized by an unusually highly methylated genome with differences in methylation patterns between MRD positive and MRD negative that can be harnessed for its potential use in prognosis and therapy.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

JIPMER.

Funding

Indian Council of Medical Research (ICMR).

Disclosure

All authors have declared no conflicts of interest.