Journal
NPJ PRECISION ONCOLOGY
Volume 7, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41698-023-00485-7
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We identified a novel fusion gene pattern NRIP1::PDGFRB in Ph-like ALL, which showed oncogenic potential in pediatric patients. The study also confirmed the inhibitory effect of multiple ABL1-specific inhibitors on this fusion gene.
Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) is a subset of ALL that demonstrated a high treatment failure rate. One of the hallmarks of Ph-like ALL is PDGFRB gene fusion, with fusion partner proteins often harboring dimerization domains and enhancing the kinase activity of PDGFRB. We determined a novel oncogenic PDGFRB fusion gene, NRIP1::PDGFRB, from a pediatric patient with ALL, encoding a protein with the carboxy-terminal kinase domain of PDGFRB, without the partner peptide. We confirmed the oncogenic potential of NRIP1::PDGFRB in vitro and the efficacy of all ABL1-specific inhibitor generations, including imatinib, dasatinib, nilotinib, and ponatinib, in suppressing this potential. PDGFRB activation mechanism may include juxtamembrane domain truncation in the predicted peptide. In conclusion, we determined a novel fusion gene pattern in Ph-like ALL.
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