Constitutional chromosome rearrangements that mimic the 2017 world health organization “acute myeloid leukemia with recurrent genetic abnormalities”: A study of three cases and review of the literature

•Recurrent genetic abnormalities exist in AML.•Germline translocations can mimic AML translocations. To identify and characterize constitutional chromosomal rearrangements that mimic recurrent genetic abnormalities in acute myeloid leukemia (AML). Bone marrow and blood chromosome studies were reviewed to identify constitutional rearrangements that resemble those designated by the 2017 revised World Health Organization (WHO) “AML with recurrent genetic abnormalities”. Mate-pair sequencing (MPseq) was performed on cases with constitutional chromosome mimics of recurrent AML abnormalities to further define the rearrangement breakpoints. Three cases with constitutional rearrangements were identified, including t(6;9)(p23;q34), inv(16)(p13.1q22), and t(9;22)(q34.1;q12.2). Two cases were bone marrow specimens being evaluated for hematologic neoplasms, while one case was a blood specimen being evaluated for primary ovarian insufficiency. MPseq provided high-resolution and precise rearrangement breakpoints, and resolved the atypical FISH results generated with each rearrangement. Our findings illustrate that constitutional rearrangements can mimic recurrent genetic abnormalities observed in AML, and we emphasize the importance of correlating genetic data with clinical and hematopathologic information.