PhD Scientific Days 2025

Poster Session II. - E: Pathological and Oncological Sciences

Investigating CD49f expression patterns and related signaling pathways in adult B-cell acute lymphoblastic leukemia

Name of the presenter

Hunyadi Anna

Institute/workplace of the presenter

Department of Pathology and Experimental Cancer Research

Authors

Anna Hunyadi¹, Ágnes Márk¹, Gábor Barna¹, Csilla Kriston¹, Gábor Szalóki¹, Balázs Kőszegi¹, Anna Rakonczai², Ilona Tárkányi², Bálint Kovalovszki³

1: Department of Pathology and Experimental Cancer Research, Semmelweis University
2: Department of Internal Medicine and Haematology, Semmelweis University
3: Aladár Petz University Teaching Hospital

Text of the abstract

Introduction: CD49f is an integrin transmembrane protein, that we have investigated in pediatric B-cell acute lymphoblastic leukemia (B-ALL): its expression is associated with poor prognosis, central nervous system (CNS) involvement and the ETV6::RUNX1 fusion gene; it is reliably expressed on malignant lymphoblasts throughout treatment, making it a useful measurable residual disease marker (MRD). B-ALL in adulthood is characterized by a worse prognosis, hence uncovering the background and mechanisms of the disease is extremely important.
Aims: We investigated CD49f expression patterns and changes in this population. We planned to compare our findings with the patients’ genetic and clinical data. Furthermore, we aimed to study the activity of signaling molecules downstream of CD49f.
Method: We analyzed the diagnostic bone marrow (BM) flow cytometry measurements of 24 patients, and 11 of them had MRD-positive follow-ups. The 3 expression categories were based on median fluorescence intensity (MFI): bright (MFI>1000), dim (100<MFI<1000), negative (MFI<100). We analyzed the following clinical data: age, CNS involvement at diagnosis and genetic data. We performed immunohistochemistry (IHC) on 10 paraffin embedded bone biopsies with Src, phosphorylated FAK (pTyr576) and ILK antibodies.
Results: 46% of the diagnostic samples were bright, 29% dim, 17% negative, and 8% partially positive, median MFI was 961. 3 patients had CNS involvement, blasts in their diagnostic BM were negative, but those in the CNS were CD49f-positive. MRD-negative patients tended to have higher CD49f expression on blasts at diagnosis (median MFI=1355) than MRD-positive patients (median MFI=151)(P=0.066). After treatment, CD49f expression of the residual blasts varied. CD49f-positivity correlated with nuclear pFAK and Src staining, but all cases were ILK-negative. CD49f expression did not show correlation with neither genetic data nor age.
Conclusion: Blasts in the CNS were CD49f-positive despite those in the BM being negative. Higher CD49f expression at diagnosis might predict lower MRD rates. CD49f expression correlated with FAK and Src activity.
Funding: SUPPORTED BY THE 2024-2.1.1-EKÖP-2024-00004 UNIVERSITY RESEARCH SCHOLARSHIP PROGRAMME OF THE MINISTRY FOR CULTURE AND INNOVATION FROM THE SOURCE OF THE NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND.