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

Objectives: To identify and characterize constitutional chromosomal rearrangements that mimic recurrent genetic abnormalities in acute myeloid leukemia (AML). Methods: 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. Results: 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. Conclusions: 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.