ETV6RUNX1

ETV6-RUNX1, also known as TEL-AML1, is a fusion gene resulting from the chromosomal translocation t(12;21)(p13;q22) that fuses the ETV6 gene on chromosome 12 with RUNX1 on chromosome 21. It is one of the most frequent genetic alterations in pediatric B-cell acute lymphoblastic leukemia (B-ALL), seen in roughly 20–25% of cases, and is associated with an unusually favorable response to modern therapy.

The fusion creates a chimeric transcription factor that disrupts normal hematopoietic differentiation. It is thought to arise in utero, establishing a preleukemic clone, with additional genetic events typically required for progression to overt leukemia.

Clinically, ETV6-RUNX1–positive ALL usually presents in children around ages 2–5. It commonly shows precursor B-cell features with CD10 positivity and variable white blood cell counts. The prognosis is generally favorable when treated with contemporary multi-agent chemotherapy, and relapse is relatively infrequent.

Diagnosis relies on molecular methods. FISH testing for the ETV6-RUNX1 fusion or RT-PCR for the fusion transcript are standard approaches, with conventional karyotyping or microarray analysis offering supportive evidence. Monitoring minimal residual disease (MRD) plays a key role in risk stratification and treatment adjustment.

Prognosis and risk stratification reflect the positive association of this fusion with treatment response. In pediatric ALL, ETV6-RUNX1 positivity correlates with high event-free survival and low relapse rates under current regimens. Adult cases exist but are less common and the data on outcomes are more variable.

Epidemiologically, the fusion is more frequent in children than adults. Research continues to elucidate leukemogenesis, the biology of the preleukemic clone, and implications for targeted or MRD-guided therapies, although standard treatment remains highly effective for many patients with this abnormality.