ETV6:RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Review
Khalid Abdelsamea Mohamedahmed
Abstract
The ETV6:RUNX1 (formerly TEL: AML1) fusion gene resulting from the cryptic translocation t (12;21) (p13; q22) represents the most frequent chimeric oncogene in pediatric B-cell precursor acute lymphoblastic leukemia (B-ALL), accounting for approximately 25% of cases. Typically initiating in utero during fetal hematopoiesis, the fusion protein establishes a covert pre-leukemic clone that persists across a variable latency period. Overt leukemogenesis necessitates secondary postnatal genomic events, such as deletions of the un-rearranged ETV6 allele, alterations in B-cell developmental genes (PAX5, EBF1), or mutations in signaling cascades (KRAS, NRAS). Although ETV6:RUNX1-positive ALL confers a distinctly favorable prognosis with longterm survival exceeding 90–95%, up to 10–15% of patients suffer late disease recurrence or treatment toxicity. This comprehensive review examines the molecular architecture of ETV6:RUNX1, its multi-step pathobiology, diagnostic methods, clinical outcomes, risk factors for relapse, and emerging targeted/ de-escalation therapeutic strategies.
