Characterization of Sole Loss of the Y Chromosome and Associated Effects on Adaptive Immunity in Adult Male Patients with Acute Myeloid Leukemia (AML)

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.4304-4304
• Main Authors: Velegraki, Maria, Wang, Cankun, Nicolet, Deedra, Mrózek, Krzysztof, Weltge, Payton, Hamp, Ethan, Buss, Jill, Laganson, Andrea, Oakes, Christopher C., Krull, Jordan, Byrd, John C., Stone, Richard M., Ma, Qin, Eisfeld, Ann-Kathrin, Li, Zihai
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-211437

Loss of the Y chromosome (LOY) is frequently found in healthy aging men, which challenged evaluation of its clinical relevance for decades. Recently, however, LOY was identified as causative event for tumorigenesis via evasion of adaptive immunity in solid tumors. In AML, sole LOY is found in about 6% of newly diagnosed AML, comprising approximately 15% of the cytogenetic abnormalities frequently detected. Thus, we set out to characterize the possible role of LOY in AML pathogenesis and clonal evolution to delineate the clinical and translational relevance of this recurrent, yet least appreciated cytogenetic abnormality in adult patients with AML. Using an integrative bioinformatics methodology, we explored the transcriptomic profile of 23 bone marrow (BM) samples from male AML patients with LOY as the sole cytogenetic abnormality and a comparison group of 218 cytogenetically normal (CN) male patients with AML. As an additional control group, we also included 203 CN BM samples from female AML patients, all of which were derived from newly diagnosed, adult AML patients who were similarly treated on Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology frontline protocols. Using DESeq2, we first identified differential gene expression patterns, including 364 genes (2.3%) that were upregulated and 74 genes (0.46%) that were downregulated in the LOY compared with the CN male samples (adj p-value