Published: 21-08-2023 08:58 | Updated: 21-08-2023 08:58

Using whole-genome sequencing in the diagnostics of acute lymphoblastic leukemia in children

Mother holding babys hand
Foto: Aditya Romansa on Unsplash

A new Swedish study shows that whole genome sequencing can detect clinically relevant genomic abnormalities in acute lymphoblastic leukemia, ALL, and has great potential to be implemented in the diagnostic setting. The study was carried out by researchers within the Clinical Genetics group at the Department of Molecular Medicine and Surgery, the Genomic Medicine Sweden for haematology and published in the scientific journal Frontiers in Oncology.

Gisela Barbany
Gisela Barbany, docent i medicinsk genetik

The impressive success story of pediatric ALL, with over 90% of the patients surviving the disease, is in part due to the classification of patients to different risk categories based on genetic findings and the initial therapy response. However, the risks of relapse or death due to treatment complications or acquiring long-term side effects are still challenging part of the therapy adjustment. Also, current genetic routine diagnostic requires a multimodal and cumbersome investigation to adequately characterize ALL samples.

“There is approximately 25% of ALL patients with no stratifying genetic markers to assign them to a risk group. Today, we need a more sensitive method to improve genetic diagnostic yield which enables us to implement a more precise treatment strategies”, says Gisela Barbany, Associate Professor and Senior Consultant at the Clinical Genetics Department, Karolinska University Hospital.

In this study, the diagnostic yield and accuracy of whole genome sequencing (WGS) was assessed as a sole diagnostic method to detect genetic lesions of clinical relevance in the diagnostic setting of ALL using a set of 88 retrospective diagnostic bone marrow samples from ALL patients.

Fatemah Rezayee
Fatemah Rezayee, doktorand vid klinisk genetik

“The results showed that WGS as a standalone method detected all clinically relevant genetic lesions. In addition, we could identify leukemic driver aberrations in 35 out of 39 patients which lacked stratifying lesions by routine diagnostics”, says Fatemah Rezayee, PhD student at the Clinical Genetics research group and first author of the publication.

The study also revealed complete concordance between the routine diagnostics and the WGS results. Moreover, the method was successful to detect challenging recurrent aberrations located in a highly repetitive regions with a tailored bioinformatic tool. The diagnostic information provided by WGS will enable the treating clinicians to accurately assign ALL patients to genetic categories and help to adjust treatment, hopefully decreasing the risk of death and long-term side effects. Overall, the authors conclude that WGS has great potential to be implemented as the sole method in clinical setting for diagnosing ALL patients.

This work was done within the Genomic Medicine Sweden for haematology, in collaboration with the SciLifeLab Clinical Genomics. The study was funded by Science for Life Laboratory Swedish Genomes Program (supported from the Knut and Alice Wallenberg Foundation), Swedish Childhood Cancer Fund (Barncancerfonden) and the Swedish Research Council grant under the frame of ERA PerMed.


Feasibility to use whole-genome sequencing as a sole diagnostic method to detect genomic aberrations in pediatric B-cell acute lymphoblastic leukemia Rezayee F, Eisfeldt J, Skaftason A, Öfverholm I, Sayyab S, Syvänen A C, Maqbool K, Lilljebjörn H, Johansson B, Olsson-Arvidsson L, Pietras C O, Staffas A, Palmqvist L, Fioretos T, Cavelier L, Fogelstrand L, Nordlund J, Wirta V, Rosenquist R and Barbany G (2023) Frontiers in Oncology DOI=10.3389/fonc.2023.1217712