Scientists from St. Jude Children’s Research Hospital, Seattle Children’s and the Children’s Oncology Group have identified genetic variations that influence relapse risk in children with standard risk B-cell acute lymphoblastic leukemia (SR B-ALL). This study, published in the Journal of Clinical Oncology, provides a basis for improved diagnosis, precise tailoring of treatment intensity and potentially the development of novel treatment approaches. Standard risk ALL has a high remission rate, but around 15% of patients experience relapse. Previous studies on relapse risk have primarily focused on high-risk ALL subgroups, while this study focused on poorly understood cases of SR B-ALL.
Genomic profiling allows scientists and clinicians to predict how patients are likely to respond to therapy, shaping the treatment of childhood ALL. The study conducted genome and transcriptome sequencing on SR B-ALL samples that relapsed and samples that remained in complete remission. They found that certain B-ALL subtypes, genetic alterations, and patterns of aneuploidy were associated with relapse risk and time to relapse. Some subtypes had a low frequency of relapse, while others were associated with an increased risk. Genetic changes within these subtypes further influenced the risk of relapse, showing that genetic variations and cancer subtypes influence relapse risk in SR B-ALL.
Charles Mullighan, co-senior author and St. Jude Comprehensive Cancer Center Deputy Director, emphasized the importance of understanding the features that influence the risk of treatment failure and disease recurrence in childhood ALL. Mignon Loh, co-senior author and leader of Seattle Children’s Cancer and Blood Disorders Center, discussed the plan to reduce conventional therapies for children with ALL in the future, aiming to accurately identify those who can be cured with less therapy. The study highlighted the importance of whole-genome sequencing in identifying high-risk features in tumor cells of children with SR ALL, allowing for increased therapy intensity and potentially leading to the development of novel, personalized treatment strategies.
The results from this collaborative study provide insights into accurately determining patient risk in B-ALL, in conjunction with traditional criteria. The study identified specific genetic alterations associated with cancer susceptibility, relapse risk, and response to therapeutics. Some B-ALL subtypes were associated with a low frequency of relapse, while others were linked to an increased risk. The specific type of genetic changes within these subtypes further influenced the risk of relapse. This work demonstrated that genetic variations within B-ALL subtypes can influence relapse risk in SR B-ALL, showing that patients classified as standard-risk can have tumors with high-risk features.
The identification of genomic predictors of relapse in SR B-ALL has the potential to improve diagnosis, tailor treatment intensity, and develop novel treatment approaches. The study conducted by scientists from St. Jude Children’s Research Hospital, Seattle Children’s, and the Children’s Oncology Group represents a significant step in understanding the features that influence the risk of treatment failure and disease recurrence in childhood ALL. The findings emphasize the importance of genomic profiling in accurately determining patient risk in B-ALL, highlighting the impact of genetic variations and cancer subtypes on relapse risk in SR B-ALL. This information could lead to improved personalized treatment strategies and better outcomes for children with SR B-ALL.
