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Targetable Kinase Gene Fusions in High Risk B-ALL
Blood; ePub 2017 Apr 13; Reshmi, Harvey, et al
A precision-medicine technique to test for and treat Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) was proven beneficial in a retrospective cohort study involving 284 individuals.
Investigators looked at frequency and spectrum of targetable genetic lesions in patients with childhood B-ALL with high-risk clinical features and/or elevated minimal residual disease after remission induction therapy. They analyzed the subset in which they saw Ph-like gene expression.
Overexpression and rearrangement of CRLF2 were identified in ~44%. Of these, ~half showed genomic alterations activating the JAK-STAT pathway.
In the remaining patients:
- ABL-class fusions were seen in ~14%; EPOR rearrangements or JAK2 fusions in ~9%; and alterations activating other JAK-STAT signaling genes in ~6%.
- Other kinases and mutations involving the Ras pathway were seen in ~5% and ~6%, respectively.
Reshmi S, Harvey R, Roberts K, et al. Targetable kinase gene fusions in high risk B-ALL: A study from the Children's Oncology Group. [Published online ahead of print April 13, 2017]. Blood. doi:10.1182/blood-2016-12-758979.