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Precision Combinatorial Immunotherapeutic Targeting of Cytokine Receptor Kinase Signaling in CRLF2-Rearranged ALL
[Technical Report, Annual Report]
COLORADO UNIV AURORA CO
Pagination or Media Count:
Ph-like ALL is a high-risk subset of B-ALL defined by an activated kinase gene expression profile similar to that of BCR-ABL1-rearranged Ph ALL and driven by a diverse range of genetic alterations that activate cytokine receptor signaling pathways. Children, AYAs, and older adults with Ph-like ALL have 60 relapse risk and experience significant leukemia-associated mortality. Approximately 50 of Ph-like ALL cases harbor rearrangements in CRLF2 CRLF2-R and frequent concomitant JAK2 point mutations. In addition to patients with Ph-like ALL, CRLF2 rearrangements usually P2RY8-CRLF2 fusions with JAK2 point mutations occur in approximately 60 of children and AYAs with trisomy 21Down Syndrome-associated ALL DS-ALL and also induce hyperactive JAKSTAT signaling. Children with DS-ALL have substantial toxicity with chemotherapy and inferior clinical outcomes.
[A, Approved For Public Release]