Philadelphia chromosome-positive acute lymphoblastic leukemia: exploring microRNA-based strategies to improve outcomes.

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is characterized by the BCR::ABL1 fusion gene resulting from the translocation t(9;22). This type of leukemia represents a biologically and clinically distinct subset of ALL, known for its aggressive nature and comparatively poor prognosis among hematologic malignancies. Although the advent of tyrosine kinase inhibitors (TKIs) has converted the therapeutic view and fulfilled short-term outcomes, resistant responses remain limited, and disease relapse, often due to BCR::ABL1 kinase domain mutations or activation of alternative signaling pathways, continues to impede long-term success. Recent findings emphasizes the essential involvement of microRNAs in leukemogenesis, TKI resistance, and the advancement of Ph+ ALL. Importantly, miR-17∼92 cluster members (such as miR-17, miR-18a, miR-20a) can prompt apoptosis by direct suppression of BCL2 in BCR::ABL1 positive cells. Moreover, epigenetic silencing of miR-203 enhances BCR::ABL1 expression, further contributing to TKI resistance. These small regulatory RNAs consequently act for promising candidates both as therapeutic targets and as prognostic biomarkers, with the potential to fill treatment gaps that persist even in the TKI era.