Optical Genome Mapping in Routine Cytogenetic Diagnosis of Acute Leukemia

SIMPLE SUMMARY: Acute leukemia is a rare but severe disease for which genetic characterization allows diagnostic and prognostic classification and therapeutic management. The aim of this prospective study was to evaluate the performance of optical genome mapping (OGM) in providing an accurate genetic description of acute leukemia. We used OGM to analyze 29 samples of all types of acute leukemia collected at the time of diagnosis and compared the results obtained from karyotype, FISH, and RT-PCR, the standard techniques of our routine procedure. Overall, the results of OGM and standard techniques were concordant in all types of acute leukemia and lead to similar patient risk stratification. In addition, OGM confirmed its better resolution and detected additional genetic alterations of clinical interest. We conclude that OGM could effectively replace standard techniques and simplify our workflow in the diagnosis of acute leukemia. ABSTRACT: Cytogenetic aberrations are found in 65% of adults and 75% of children with acute leukemia. Specific aberrations are used as markers for the prognostic stratification of patients. The current standard cytogenetic procedure for acute leukemias is karyotyping in combination with FISH and RT-PCR. Optical genome mapping (OGM) is a new technology providing a precise identification of chromosomal abnormalities in a single approach. In our prospective study, the results obtained using OGM and standard techniques were compared in 29 cases of acute myeloid (AML) or lymphoblastic leukemia (ALL). OGM detected 73% (53/73) of abnormalities identified by standard methods. In AML cases, two single clones and three subclones were missed by OGM, but the assignment of patients to cytogenetic risk groups was concordant in all patients. OGM identified additional abnormalities in six cases, including one cryptic structural variant of clinical interest and two subclones. In B-ALL cases, OGM correctly detected all relevant aberrations and revealed additional potentially targetable alterations. In T-ALL cases, OGM characterized a complex karyotype in one case and identified additional abnormalities in two others. In conclusion, OGM is an attractive alternative to current multiple cytogenetic testing in acute leukemia that simplifies the procedure and reduces costs.