(680.12) Non-coding FLT3 Mutation is Associated with Lower Galectin Levels in Breast Cancer Patients

Poster Board Number: A487

Avery Funkhouser (University of South Carolina School of Medicine Greenville), Bailey Blair (University of South Carolina School of Medicine Greenville), Jane Goodwin (University of South Carolina School of Medicine Greenville), Alec Strigenz (University of South Carolina School of Medicine Greenville), Julie Martin (Prisma Health), Christopher Funk (Emory University School of Medicine), W Jeffery Edenfield (Prisma Health), Anna Blenda (University of South Carolina School of Medicine Greenville, University of South Carolina School of Medicine Greenville)

Fms Related Receptor Tyrosine Kinase 3 (FLT3) is a class III Receptor Tyrosine Kinase (RTK) which binds to the cytokine Flt3 ligand. It acts to promote cell survival, proliferation, and differentiation of hematopoietic stem cells, and is implicated in the development of acute myeloid leukemia. Galectins are a family of β-galactoside binding proteins which are involved in many cellular pathways including apoptosis and cell migration as well as the innate immune system. Previous studies have shown that galectins are upregulated and aid in cancer pathologies and current clinical trials are underway to use galectin inhibitors in cancer therapy. RTKs are known to have a variety of direct and indirect interactions with galectins. We have found that breast cancer patients with non-coding mutations of the FLT3 gene have serum concentrations of galectins -1 and -9 that align with published healthy values, compared to other breast cancer patients without the mutation which had significantly elevated levels of these galectins. Concentrations of galectin-1 and -9 of 40 breast cancer patients were measured by ELISA. Analysis of 2,800 COSMIC mutations from 50 oncogenes and tumor suppressor genes from the same patients was conducted using multiplex PCR. Correlations between the galectin serum levels and mutation presence were elucidated by statistical analysis. We found that mean levels of galectin-1 and -9 were at 23.4 ng/mL and 8.4 ng/mL respectively in breast cancer patients. However, patients with a non-coding FLT3 mutation had levels of galectin-1 (mean 16.2 ng/mL) and galectin-9 (mean 5.0 ng/mL) significantly lower than those in cancer patients without the mutation (p-value, 0.0392 and 0.0266 respectively). Moreover, they were similar to previously published galectin values for healthy controls (18.1 ng/mL and 7.0 ng/mL respectively). While galectins are known to influence spatial organization and trafficking of this class of RTKs, no specific relationship has been elucidated between galectins -1 and -9 and FLT3. Our results indicate a potential interaction of clinical significance between FLT3 and galectins -1 and -9, the mechanism of which needs to be investigated further.

Prisma Health Cancer Institute Philanthropy Grant, Sargent Foundation