#00066754

An 82-year-old man presented with progressive dyspnea. Peripheral blood showed leukocytosis (white blood cell, 80 × 10⁹/L), anemia (hemoglobin, 8.9 g/dL), thrombocytopenia (platelets, 31 × 10⁹/L), and 35% blasts (panel A, Wright-Giemsa stain, 100× objective). Bone marrow was hypercellular (90%) with 70% blasts (panel B, hematoxylin and eosin stain, 40× objective). The blasts were large with moderate cytoplasm, and some had cytoplasmic vacuoles and/or Auer rods (panel C, Wright-Giemsa stain, 100× objective). Flow cytometry identified a CD45-dim blast population (32%) expressing CD33, CD117, CD123, HLA-DR, and myeloperoxidase, with partial expression of CD4, CD13, CD34, and CD64. The patient was diagnosed with acute myeloid leukemia (AML). Conventional cytogenetics revealed 47,XY,+r[20]. Fluorescence in situ hybridization using a MYC break-apart probe demonstrated MYC amplification on the ring chromosome (panel D). Optical genome mapping (OGM) delineated highly complex rearrangements confined to chromosome 8q24.13-q24.21 (125 660 026-129 644 218; panel E), including 13 structural variants (6 duplications, 3 inversions, 3 deletions, and 1 insertion; panel F), 2 intrachromosomal rearrangements, and amplification encompassing the MYC locus (copy number, 24; panel G), consistent with chromoanagenesis. Targeted next-generation sequencing detected ASXL1 c.1723C>T (variant allele frequency [VAF], 38%) and TET2 c.2656C>T (VAF, 30%) mutations. The patient achieved complete remission with azacitidine and venetoclax, but relapsed after 2 months and died 5 months after diagnosis.

Ring chromosomes can serve as large carriers of amplified extrachromosomal DNA harboring oncogenes. OGM resolved the complex genomic architecture of a MYC-amplified ring chromosome, demonstrated its origin through chromoanagenesis, and provided evidence supporting its classification as high-risk AML.

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