Optical Genome Mapping in Newly Diagnosed Chronic Lymphocytic Leukemia
Authors: Erdem Simge , Bayrak Tokaç Ayşe Gül , Aday Aynur , Karaca Dilan , Öztürk Şükrü , Çefle Kıvanç , Yenerel Mustafa , Beşışık Sevgi 
Published: December 2024

Introduction: Chronic Lymphocytic Leukemia (CLL) is a heterogeneous neoplasm originating from B cells, accounting for approximately 30% of adult leukemias. One-third of newly diagnosed patients do not need treatment, while the remainder require treatment within a few years. Genetic abnormalities are crucial for predicting the prognosis of CLL and play an important role in determining the appropriate treatment approaches. Fluorescence in situ hybridization (FISH) is the most effective test for detecting these abnormalities. Recently, Optical Genome Mapping (OGM) has been introduced, providing a more sensitive cytogenetic approach in the diagnosis and treatment of neoplasms.
Methods: This study compared FISH and OGM results of 10 newly diagnosed CLL patients in the Department of Hematology at Istanbul University Istanbul Faculty of Medicine. FISH and OGM studies were performed on peripheral blood samples. A CLL panel including del(13q), del(11q)(ATM deletion), del(17p)(P53 deletion), IGH rearrangements, del(6q)(MYB deletion), and trisomy 12 were applied in the FISH analysis. DNA isolation from the peripheral blood samples and labeling-staining experiments were performed using the SP Blood and Cell Culture DNA Isolation Kit and Direct Labeling and Staining (DLS) Kits. A labeled gDNA solution was loaded onto the Saphyr chip and scanned on the Saphyr instrument. Data were analyzed using Bionano Access software (v1.7.2).
Results: The mean age of patients was 62.5±11.66 years, with 7 females and 3 males. According to the FISH results, the abnormalities detected in the patients were as follows: del(13q) (16%) in patient 1; del(13q) (93%) in patient 2; del(13q) (80%) in patient 4; trisomy 12 (65%) in patient 5; del(13q) (14%) in patient 6; biallelic del(13q) (26%) in patient 7; and del(13q) (33%) in patient 9. No abnormalities were detected in patients 3, 8, and 10.
According to the OGM results, the abnormalities detected in addition to those detected by FISH were: deletion (14q) in patient 1; inversion (3) and inversion (12) in patient 2; deletion (22q) and t(9;13) in patient 4; gain (2p) and inversion (3q) in patient 5; loss of X in patient 6; inversion (13) in patient 7; and gain 1p36.21 in patient 9. In patient 3, no structural variant was detected by OGM, and no abnormality was detected by FISH. Deletion (13q), deletion (22q), t(2;10), t(10;14), and gain 10q structural variants were detected by OGM in patients 8 and 10, in whom no abnormality was detected by FISH. These findings are preliminary data for our study.
Discussion: All abnormalities detected by FISH were also identified by OGM. Additionally, OGM detected del(13q) in a patient (patient 8) who was normal according to FISH. Other abnormalities detected by OGM included chromosomes not covered by the CLL FISH panel. As FISH is a target-specific method, it only provides information on the regions examined. In contrast, OGM offers comprehensive genomic information and higher sensitivity compared to conventional methods. The use of OGM in the diagnosis and treatment of heterogeneous diseases such as hematologic neoplasms will enhance the identification of new biomarkers and contribute to the development of novel diagnostic, prognostic and therapeutic approaches.