ROR1 expression and function in B-cell malignancies

Aberrant tyrosine kinase activity drives the development of many leukemias. To identify viability‑dependent kinases in acute lymphoblastic leukemia (ALL), we applied an RNAi‑assisted protein target identification (RAPID) assay across cytogenetic subtypes. In t(1;19) pediatric ALL, which produces the E2A‑PBX1 fusion, we identified the receptor tyrosine kinase ROR1 as uniquely essential for cell survival. We also found that t(1;19) ALL cells are highly sensitive to the kinase inhibitor dasatinib, which targets key mediators of pre‑B‑cell receptor (pre‑BCR) signaling. ROR1 and the pre‑BCR activate compensatory pathways, suggesting that dual‑pathway inhibition may offer an optimized therapeutic strategy.