Abstract 5145: E-selectin binding is enriched within B-cell acute lymphoblastic leukemia compared to healthy lymphoid precursors

Abstract Background: Adhesion molecules within the bone marrow vascular niche govern the self-renewal, differentiation, and proliferation of hematopoietic progenitors. Among these, E-selectin, a lectin expressed by endothelial cells which binds to the tetrasaccharide known as sialyl Lewis X (sLeX), promotes dormancy, self-renewal, and chemoresistance in native hematopoietic stem cells (HSCs). However, leukemic blasts hijack these signals, fueling their proliferation. While therapeutic disruption of E-selectin binding to its ligands has demonstrated clinical activity in acute myeloid leukemia, its role in B-cell acute lymphoblastic leukemia (B-ALL) remains underexplored. Identifying E-selectin ligands and associated downstream molecular effectors in B-ALL holds potential to reveal targetable mediators of leukemia-initiating capacity, drug tolerance, and persistence. Methods: Fresh peripheral blood and bone marrow from appropriately consented healthy donors (n=9) and clinically annotated patients (n=11) with BCR::ABL1 B-ALL identically treated on a clinical trial (NCT03595917) were profiled for sLeX expression and E-selectin binding by flow cytometry using HECA-452 monoclonal antibody and E-selectin-Ig chimera (E-Ig) respectively, along with glycoproteomic analyses. Expression of canonical E-selectin ligands (HCELL/CD44, CLA/PSGL-1, CD43E/CD43) and B cell developmental markers (CD45, CD34, CD10, CD19, CD20, CD22) were also assessed. Results: SLeX expression and E-selectin binding varied between native antigen-independent B cell developmental stages (p < 0.05). Malignant CD19+ B cells from the bone marrow of treatment-naïve B-ALL patients exhibited increased sLeX expression (p < 0.05) and a nominal increase in E-selectin binding compared to counterparts from healthy donors. E-Ig-reactive CD19+ B-ALL cells display higher CD43 expression and lower CD44 and PSGL-1 expression than E-Ig-reactive CD19+ healthy donor B cells (p < 0.05). Treatment-naïve leukemic progenitors displayed greater sLeX expression and E-selectin binding than patient-matched non-malignant populations (p < 0.05). Leukemic progenitors isolated from serial bone marrow specimens exhibited a nominal increase in sLeX expression and E-selectin binding at progression versus baseline. Conclusions: Within the lymphoid lineage, E-selectin binding is developmentally determined and enriched in malignant compared to native cells. Interrogation of downstream effectors and functional phenotypes is ongoing. Citation Format: Chase M. Weizer, Rachel A. Kraan, Evan Ales, Stella L. Jaeckle, Julia H. Keating, Marlise R. Luskin, Robert Sackstein, Mark A. Murakami. E-selectin binding is enriched within B-cell acute lymphoblastic leukemia compared to healthy lymphoid precursors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5145.