The ETV6::NCOA2 Fusion, a Recurrent Cytogenetic Abnormality in Childhood Leukemia With Defining Properties.

Abstract

t(8;12)(q13;p13)(ETV6::NCOA2) is a rare but recurrent cytogenetic abnormality in childhood leukemia with mixed myeloid/T-cell lineage. We hereby present the first pediatric B-ALL with ETV6::NCOA2. A 5-year-old boy presented with B-ALL residual disease at end-of-induction. He achieved complete remission after therapy intensification, but relapsed 2 months later. Karyotype at relapse showed 46,XY,del(6)(q21q23),t(8;12)(q13;p13),-9,+mar[17]. ETV6::NCOA2 was confirmed by FISH and RT-PCR. Next-generation sequencing revealed a pathogenic NRAS variant. The patient developed severe neutropenia, complicated by bacterial sepsis and death 10 months later. Unlike cases with mixed myeloid/T-cell phenotype, no NOTCH1 mutations were detected. Review of published cases suggests that the presence of additional cytogenetic abnormalities dictates adverse prognosis.