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Genetic Impact on ALL Treatment-Related Relapse
Leukemia; ePub 2017 Feb 10; Karol, Larsen, et al
Inherited genetic variation contributes to treatment-related relapse risk in children with acute lymphoblastic leukemia (ALL), according to a study involving more than 2,200 individuals.
Investigators looked at how germline genetic factors impacted relapse in participants from the Children’s Oncology Group trial. They also tested for replication of relapse-associated single-nucleotide polymorphisms (SNPs) in external data sets of antileukemic drug pharmacokinetics and pharmacodynamics, as well as an independent cohort. Among the results:
- After adjusting for treatment and ancestry, there were 302 germline SNPs linked with relapse.
- 715 additional SNPs were linked with relapse in an ancestry-specific manner.
- 224 of the relapse-associated SNPs were linked with rapid drug clearance or drug resistance; 32 were replicated in the independent cohort.
- 20/54 SNPs linked with asparaginase resistance or allergy were seen in a Capizzi-methorexate subgroup, vs 8/54 in a high-dose methotrexate arm.
Karol S, Larsen E, Cheng C, et al. Genetics of ancestry-specific risk for relapse in acute lymphoblastic leukemia. [Published online ahead of print February 10, 2017]. Leukemia. doi:10.1038/leu.2017.24.