MYC and KMT2A multiple extra copies in acute myeloid leukemia

An 80-year-old woman with a prior history of thyroid cancer cured with surgery and ionizing radiation therapy presented with asthenia, weight loss, and chest tightness. A complete blood count revealed bicytopenia (hemoglobin, 5.0 g/dL; platelets, 42 × 10⁹/L), and peripheral blood smear examination showed 14% blasts. The bone marrow was infiltrated by 35% blasts and showed multilineage dysplasia. Immunophenotyping analysis showed positivity for MPO, CD34, CD33, CD117, CD36, CD71, and CD38; aberrant positivity for CD2, CD4, and CD7; and negativity for cCD3 and CD19. These results led to a diagnosis of therapy-related acute myeloid leukemia. Cytogenetic analysis revealed a complex karyotype, which was, according to the 2016 International System for Human Cytogenetic Nomenclature, described as: 44,XX,dic(5;18)(q11;p11),add(8)(q24),dic(11;16)(q11;p11),del(12)(p11p13)[2]/45,sl,+r[10]/46,sdl1,+r[6]/ 47,sdl2,+9[2] (panel B, conventional karyotype, R-banding). Interestingly, fluorescence in situ hybridization analysis revealed a concurrent gain of multiple extra copies of 2 genes, MYC (6 copies) and KMT2A (8 copies), in the additional material in 8q24 and in ring chromosomes (panel A, fluorescence in situ hybridization original magnification ×1000, MYC dual color break-apart probe [orange arrows] and KMT2A-MLLT3 dual color fusion probe [green arrows for KMT2A]).The patient was treated with azacitidine.

Single gene gain of multiple extra copies or amplification is already a rare phenomenon in acute myeloid leukemia (<1%), associated with poor prognosis, but concurrent gain of multiple extra copies of 2 genes in the same clone is exceptional.