A Case of Cryptic CBFB::MYH11 Acute Myeloid Leukemia With Noncanonical Breakpoints Detected by Optical Genome Mapping

作者：Eduardo Edelman Saul, Samuel Urrutia, Hui Yang, Guillermo Montalban‐Bravo, Guilin Tang, Gökçe Törüner, Keyur P. Patel, Rajyalakshmi Luthra, Carlos E. Bueso‐Ramos, Sa A. Wang, Kelly S. Chien, Koji Sasaki, Himachandana Atluri, Hannah Goulart, Beenu Thakral, Guillermo Garcia‐Manero, Rashmi Kanagal‐Shamanna · 发表于：Journal of the National Comprehensive Cancer Network · 年份：2025 · DOI：10.6004/jnccn.2025.7015 · 被引用次数：4 · 研究领域：Acute Myeloid Leukemia Research、Advanced biosensing and bioanalysis techniques、Cancer Genomics and Diagnostics

Accurate and timely detection of clinically relevant genetic abnormalities, such as CBFB::MYH11 or inversion(16) [inv(16)], is critical for the diagnosis and management of patients with acute myeloid leukemia (AML). Notably, CBFB::MYH11 is a disease-defining mutation in AML and is associated with a favorable prognosis. The current standard-of-care workup, which includes a combination of conventional G-banding karyotyping, fluorescence in situ hybridization (FISH), and/or reverse-transcriptase PCR, poses challenges in detecting variant CBFB::MYH11 translocations. High-resolution, genome-wide technologies capable of accurate and unbiased detection of chromosomal structural aberrations at the gene/exon level, such as optical genome mapping (OGM), will be helpful for the timely detection of clinically actionable abnormalities. This case report presents a patient initially diagnosed with therapy-related myelodysplastic syndrome (MDS) following cytotoxic therapy and treated with a hypomethylating agent, who later experienced progression to AML with CBFB::MYH11. Retrospective analysis of the initial diagnostic sample using OGM revealed a cryptic CBFB::MYH11 abnormality at the time of the first presentation. Furthermore, OGM enabled comprehensive characterization of this novel CBFB::MYH11 transcript with noncanonical breakpoints, which were not detected by standard molecular techniques. This case highlights a critical diagnostic blind spot in the detection of CBF::MYH11 AML, represen...