Abstract C015: Unraveling the structure of the Philadelphia chromosome using super-resolution microscopy

Abstract Philadelphia-positive leukemia is characterized by the translocation t(9;22)(q34;q11), which results in the oncogene BCR-ABL1 and a chromosome called the Philadelphia (Ph) chromosome (chr). The Philadelphia chromosome is best characterized in Chronic Myeloid Leukemia (CML); however, the translocation is also found in Acute Lymphoblastic Leukemia (ALL). Philadelphia-positive ALL has been historically understudied, especially in minority populations. Genome organization is a highly complex process by which chromatin is segregated within the nucleus into specific domains, making stable translocations highly unfavorable. How translocations are stabilized has been historically understudied. Here, we aim to examine how the Ph chr is stabilized and be the first to visualize an entire abnormal chr with high spatial and genomic resolution at the single-cell level. Using OligoSTORM, a super-resolution microscopy technique, we aim to image the entirety of the Ph chr at a nanoscale resolution in both CML and ALL cell lines. In addition to the DNA super-resolution trace, we have designed an RNA library to image a series of RNAs from the Ph chr on the same sample as the DNA trace, allowing us to connect the transcriptional data to the chromatin structure. We have successfully traced the entirety of the Ph chr. We have preliminary data suggesting that chr9 and chr22 segregate close to each other in non-leukemia healthy cells. We have also proven that our library design and methodology work to achieve the primary 500kb resolution. Preliminary data suggests that chr9 and chr22 in cells, that don’t typically have a Ph chr, segregate within proximity to translocate successfully. This study aims to compare the 3D structure of CML, ALL and non-leukemia cell lines to potentially identify genome organization-based biomarkers for identify and targeting the Philadelphia chromosome. Citation Format: Gabrielle S. Dewson, Guy Nir. Unraveling the structure of the Philadelphia chromosome using super-resolution microscopy [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C015.