Evaluation of Optical Genome Mapping in Phi Negative Myeloproliferative Neoplasia in the Detection of Acquired Cytogenetic Abnormalities
Key claim: Optical genome mapping (OGM) is being prospectively evaluated in Ph-negative MPN patients as a higher-sensitivity alternative to standard cytogenetics (CBA+/-FISH) for detecting acquired structural and copy-number chromosomal abnormalities.
Abstract
Standard cytogenetics (CBA +/- FISH) is of diagnostic and prognostic interest in Ph- MPN. However, its value is limited by the low frequency of detected abnormalities. The development of tools to increase the sensitivity of detection of chromosomal alterations is therefore particularly adapted to these pathologies. Optical genome mapping (OGM) is a high resolution “long read” technique that allows the identification of structural and copy number variations at the whole genome level. Several recent studies suggest that OGM is a future tool for cytogenetic characterization of haematological disorders. Its ability to describe structural abnormalities, including balanced ones, represents a major advantage over currently used technologies. Thus, OGM seems to be the key tool for cytogenetics of haematological malignancies in the coming years, making it possible to replace, under certain conditions, not only karyotype and FISH, but CMA and even RT-MLPA for the search for fusion transcripts, thus filling in the gaps in these techniques while maintaining their advantages.
To define the place of this technology in Ph- MPN, the investigators will perform a OGM analysis on patients with Ph-MPN for whom bone marrow exploration is scheduled. These results will be compared with those of standard cytogenetics (CBA +/- FISH).
Why this matters
Cytogenetic abnormalities inform risk stratification and transformation prediction across Ph-negative MPNs (notably PMF via MIPSS70+v2/GIPSS, but also PV and ET), yet standard CBA±FISH has limited sensitivity for cryptic structural variants and sub-karyotypic CNVs. Prospectively benchmarking optical genome mapping against conventional cytogenetics in this disease context could reclassify a subset of patients as cytogenetically abnormal and sharpen subtype-specific prognostic models. If validated, OGM could become a unifying genomic adjunct across MPN subtypes for natural-history tracking and progression detection.