Novel Cytogenetic Findings in a Case of Mixed Phenotype Acute Leukemia within the Context of a Complex Karyotype

Mixed phenotype acute leukemia (MPAL) is a rare hematological malignancy characterized by combinatorial aberrations involving cells of the myeloid, T-, and/or B- lineages, most often diagnosed by means of immunophenotyping in order to assess lineage-specific markers, which can still yield inconclusive diagnoses. MPAL with a complex karyotype (three or more chromosomal abnormalities) is a cytogenetic subtype of MPAL associated with a poor prognosis, but limited data is available about the cytogenetic abnormalities present in this context.

Herein, we present the case of a 67-year-old female whose bone marrow biopsy revealed an extensive blast population showing dual morphologic differentiation, including lymphoblasts and larger myeloblasts with monocytic differentiation. Multiparametric immunophenotyping by flow cytometry revealed a blast population that was positive for CD45, CD19, CD22, CD34, CD38, and HLA-DR. The blast populations were also immunereactive for both myeloperoxidase and TdT; thus, a diagnosis of mixed phenotype acute leukemia was rendered. Conventional cytogenetic analysis revealed a hyperdiploid composite karyotype with numerical abnormalities involving chromosomes 2, 6, 8, 10, 11, 14, 19, 20, 21, and 22, as well as structural abnormalities involving 1p, 1q, 9p, 16p, 17p, 19q, 20q, and a marker chromosome. Concurrent interphase and metaphase FISH studies were able to detect a deletion of CDKN2A/p16 at 9p21 and corroborated the presence of extra copies of chromosomes 8, 11, 20, and 22.

This case provides further insight into the plethora of cytogenetic abnormalities not involving BCR-ABL1 and/or MLL present in MPAL with a complex karyotype and adds to the pool of cytogenetic information about this rare subset of hematological malignancies.