The outcome for adolescents and young adults with acute lymphoblastic leukemia (ALL) is inferior to that in children, and the outcome for children with ALL who experience relapse is dismal. Therefore, new therapeutic options are urgently needed to improve survival rates for this high-risk ALL population.

Genomic Landscape

In our comprehensive study—reviewed in this issue of The ASCO Post—we have shown for the first time that Philadelphia chromosome–like ALL accounts for almost 15% of children with high-risk ALL and over one-quarter of young adults with ALL.¹ Furthermore, patients with Philadelphia chromosome–like ALL have significantly inferior event-free and overall survival rates compared to those without the disorder in all ages studied.

By performing comprehensive genomic analysis on a large number of Philadelphia chromosome–like ALL cases (> 150), we have shown that a majority of these patients harbor alterations activating tyrosine kinase or cytokine receptor signaling. Moreover, we have identified subgroups within Philadelphia chromosome–like ALL based on the genes that were altered. Understanding the genomic landscape of Philadelphia chromosome–like ALL has guided the development of screening tests to identify these patients at diagnosis.

Effective Targeting

Importantly, we have shown that a majority of the genetic lesions present in Philadelphia chromosome–like ALL can be effectively targeted with a limited number of U.S. Food and Drug Administration–approved tyrosine kinase inhibitors, including dasatinib (Sprycel) for ABL1-class alterations and ruxolitinib (Jakafi) for JAK-activating lesions. Thus, this study has the potential to improve the clinical management of Philadelphia chromosome–like ALL patients by enabling rapid identification of these patients at diagnosis and providing new therapeutic options.

The addition of molecularly targeted therapies to current chemotherapy regimens will likely improve survival rates for a significant proportion of children, adolescents, and young adults with ALL who would otherwise have a high rate of treatment failure and relapse. Several clinical trials are currently being developed to formally assess the efficacy of tyrosine kinase inhibitors in Philadelphia chromosome–like ALL. ■

Disclosure: Dr. Roberts is a lead author of the study reported in The New England Journal of Medicine and reviewed in this issue of The ASCO Post.

Reference

1. Roberts KG, Li Y, Payne-Turner D, et al: Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med 371:1005-1015, 2014.

Dr. Roberts is a Postdoctoral Research Associate in the Department of Pathology, St. Jude Children’s Research Hospital, Memphis.