Myeloid neoplasms associated with t(3;12)(q26.2;p13) are clinically aggressive, show myelodysplasia, and frequently harbor chromosome 7 abnormalities

Sporadic reports of t(3;12)(q26.2;p13) indicate that this abnormality is associated with myeloid neoplasms, myelodysplasia, and a poor prognosis. To better characterize neoplasms with this abnormality, we assessed 20 patients utilizing clinicopathological data, cytogenetic, and targeted next-generation sequencing analysis. We also performed literature review of 58 prior reported cases. Patients included ten men and ten women with median age 55.8 years (range, 27.8–78.8). Diagnoses included 11 acute myeloid leukemia (AML, 5 de novo and 6 secondary), 5 myelodysplastic syndromes (MDS, 3 de novo excess blasts-2 and 2 therapy-related), 2 chronic myeloid leukemia BCR-ABL1-positive blast phase (1 de novo and 1 secondary), 1 primary myelofibrosis (secondary), and 1 mixed-phenotype acute leukemia T/myeloid (MPAL, secondary). Morphologic dysplasia was identified in all AML cases (5/5), MDS cases (4/4), therapy-related cases (3/3), half of myeloproliferative neoplasm cases (1/2), and one MPAL case assessed. The t(3;12) was detected de novo and in subsequent workups in 9 and 11 patients, respectively. Seven patients had t(3;12) only and eight patients had additional chromosome 7 abnormalities. Fluorescence in-situ hybridization detected MECOM (n = 11) and ETV6 (n = 7) rearrangements in all cases assessed. FLT3 internal tandem duplication was identified in five (25%) patients. We identified 13 genetic abnormalities in the de novo group (n = 9), and 25 in the secondary disease group (n = 11). All patients received chemotherapy, with seven allogeneic and two autologous stem cell transplantations. At last follow-up, 14 (70%) patients died with median survival of 6.3 months (range, 0.1–17.3) after detection of t(3;12). In summary, t(3;12)(q26.2;p13) is a rare cytogenetic abnormality in myeloid neoplasms. Myelodysplasia, chromosome 7 abnormalities, and high blast counts are common, and the prognosis is poor. Given the close relationship between the presence of this cytogenetic abnormality and the MDS-related changes, we recommend adding t(3;12)(q26.2;p13) to the list of AML with myelodysplasia-related changes defining abnormalities of the World Health Organization 2017 classification of myeloid neoplasms.