ETV6 rearrangements are recurrent in myeloid malignancies and are frequently associated with other genetic events.

ETV6 (TEL) rearrangements are favorable in pediatric acute lymphoblastic leukemia but are less well characterized in myeloid malignancies. We investigated 9,550 patients with myeloid disorders for ETV6 rearrangements by chromosome banding analysis and interphase fluorescence in situ hybridization. ETV6 rearrangements were identified in 51 of 9,550 (0.5%) patients (range, 19.2-85.3 years). Frequencies were in detail: acute myeloid leukemia (AML): 40 of 3,798, 1.1%; myelodysplastic syndromes (MDS): 6 of 3,375, 0.2%; myeloproliferative neoplasms (MPNs): 5 of 1,720, 0.3%; MDS/MPN: 0 of 210; and chronic myelomonocytic leukemia: 0 of 447. Thirty-three different partner bands of ETV6 were identified, and most were recurrent: 3q26 (n = 10), 5q33 (n = 4), 17q11 (n = 3), 22q12 (n = 3), 5q31 (n = 2), and 2q31 (n = 2). Additional chromosomal abnormalities were identified in 29 of 51 (57%) ETV6 rearranged cases. In AML, ETV6 rearrangements were frequently associated with NPM1 (9/39, 23%) and RUNX1 mutations (6/31, 19%). The FAB M0 subtype was more frequent in ETV6 rearranged de novo AML than other AML (P < 0.001); expression of CD7 and CD34 by immunophenotyping was higher in ETV6 rearranged AML compared with other subgroups. Survival of 29 ETV6 rearranged de novo AML was compared with 818 AML from other cytogenetic subgroups. Median overall and event-free survival of ETV6 rearranged cases was similar to the intermediate-risk cohort (26.3 vs. 62.2 months and 14.0 vs. 15.4 months) defined according to Medical Research Council criteria. Our study confirms the variety of ETV6 rearrangements in AML, MDS, and MPNs often in association with other genetic events. Prognosis of ETV6 rearranged de novo AML seems to be intermediate, which should be independently confirmed.