Rare Ring Chromosome [r(15)]: Cytogenetic Abnormality in TP53-Mutated De Novo AML-M4 Masked as Gastrointestinal Bleed With Rapidly Progressing Hyperleukocytosis and Leukostasis

Abstract

TP53-mutated (TP53m) acute myeloid leukemia (AML) comprises only 5-15% of de novo AML, associated with poor survival outcomes due to its resistance to conventional therapy. Ring chromosomes, an even more rare subset of genetic anomalies, occur in only 2% of cases. We report a unique case of de novo AML with both TP53 and ring chromosome anomalies leading to a catastrophic outcome in a 72-year-old male who initially presented with gastrointestinal bleeding (GIB) and urethral stone status post-cystoscopy with Jstent placement. He had no history of chemotherapy use, radiation, benzene exposure, or any other risk factors except for his age. He was noted to have pancytopenia, for which bone marrow biopsy, flow cytometry, and cytogenetic studies were done. Biopsy reported an interesting next-generation sequenced TP53-mutated AML, which correlates with a low rate of response to standard chemotherapy except for bone marrow transplants. Notably, with a complex aberration of 45 XY with multiple translocations (t), deletions (del), inversions (inv), derivative (der) breakpoints, aneuploidy, and rare ring and maker chromosomes, his case was complicated with rapid-onset and very severe hyperleucostasis, reflecting the prognostic value of this rare cytogenetic configuration. The patient expired within 48 hours of diagnosis, despite the urgent initiation of cytoreductive therapy and the mitigation of tumor lysis syndrome with Rasburicase. To the best of our knowledge, this is one of the first AML-M4 patients with rapid-onset leucostasis and the demise of next-generation sequences (NGS) in a de Novo AML patient with this rare complex combination.