Discipline: Biological Sciences
Subcategory: Cancer Research
Room: Exhibit Hall
Valeria Brown - Tougaloo College
Co-Author(s): Diana O Treaba, Rhode Island Hospital; Dennis M Bonal, Rhode Island Hospital; Anna Chorzalska, Rhode Island Hospital; Alissa Oakes, Rhode Island Hospital; Makayla Pardo, Rhode Island Hospital; Max Petersen, Rhode Island Hospital; Christoph Schorl, Rhode Island Hospital; Kelsey Hopkins, Rhode Island Hospital; Dean Melcher, Rhode Island Hospital; Ting C. Zhao, Rhode Island Hospital; Olin Liang, Rhode Island Hospital; Eui-Young So, Rhode Island Hospital; John Reagan, Rhode Island Hospital; Adam J Olszewski, Rhode Island Hospital; Jim Butera, Rhode Island Hospital; Douglas C. Anthony, Rhode Island Hospital; Peter Rintels, Rhode Island Hospital; Peter Quesenberry, Rhode Island Hospital; Patrycja M Dubielecka, Rhode Island Hospital
Acute myeloid Leukemia (AML) is a genetically heterogenous malignancy with an overall 5-year survival rate of approximately 26% due to poor treatment responses. Recent studies have shown possible involvement of the non-hematopoietic compartment in AML development and AML-specific remodeling of the bone marrow (BM) microenvironment. However, our understanding of these BM microenvironmental changes, specifically upon chemotherapeutic treatment, are limited. Thus, we comparatively examined differential gene expression within the core BM biopsies of patients classified as responders or non-responders to standard of care treatment with cytarabine and daunorubicin. We found that patients that respond to chemotherapy showed significant reactivation of mesenchymal stromal cells within the BM microenvironment, whereas patients that showed sub-optimal response showed significant reactivation of osteo-committed subfraction of mesenchymal cells. We identified surface markers specific to mesenchymal reactivation in the stroma including PVR (Poliovirus Receptor Cell Adhesion Molecule), CD271 (Nerve Growth Factor Receptor), and PDGFRβ (Platelet Derived Growth Factor Receptor Beta). The following markers were found to be upregulated in osteo-committed subfraction of mesenchymal cells in non-responders: SDC4 (Syndecan 4), CDH2 (Cadherin 2), and CADM1 (Cell Adhesion Molecule 1). We are now further validating these markers using fibroblasts, human mesenchymal stem cells, and osteoblasts with RT-PCR and flow cytometry as well as immunohistochemistry. Identifying markers specific to response to chemotherapy may potentially aid in identification of new therapeutic targets within the AML BM microenvironment.
Funder Acknowledgement(s): NIGMS P20GM119943, Brown Physician C-TRI Award,Legorreta Cancer Center Pilot Grant
Faculty Advisor: Dr. Patrycja Dubielecka, firstname.lastname@example.org
Role: During the summer of my junior year, I interned in Dr. Patrycja Dubielecka-Szczerba’s laboratory at the Lifespan Hospital. Using qPCR, our data has so far validated the majority of our markers to help better understand AML patient responsiveness to chemotherapeutics and identify new potential therapeutic targets within the AML BM microenvironment.