PhD Scientific Days 2026

Poster Session 1.D - Pathological and Oncological Sciences

Prognostic value of ITGA6 mRNA isoforms and association with surface CD49f expression in pediatric B-cell acute lymphoblastic leukemia

Name of the presenter

Hunyadi, Anna

Institute/workplace of the presenter

Department of Pathology and Experimental Cancer Research, Semmelweis University

Authors

Anna Hunyadi¹, Lili Anna Kenéz¹, Gábor Barna¹, Gábor Szalóki¹, Csilla Kriston¹, Zsolt Komlósi², Dániel Erdélyi³, Krisztina Csanádi⁴, Ágnes Márk¹
1: Department of Pathology and Experimental Cancer Research, Semmelweis University
2: Institute of Genetics, Cell- and Immunobiology, Semmelweis University
3: Pediatric Center, Tűzoltó Street Department, Semmelweis University
4: Heim Pál National Pediatric Institute

Text of the abstract

Introduction:B-cell acute lymphoblastic leukemia (B-ALL) is one of the most common childhood malignancies. Although CD49f integrin is frequently overexpressed on blasts, its specific role remains unclear. Its two mRNA isoforms (ITGA6A/B) have never been investigated in B-ALL.
Method:We analyzed samples from 46 pediatric B-ALL patients: diagnostic (n=39) and relapsed (n=7); bone marrow (n=37) and peripheral blood (n=9) samples. Bone marrow samples from these patients at day 15 were available in 38 cases. We determined cell surface CD49f (sCD49f) expression on malignant lymphoblasts with flow cytometry, using median fluorescence intensity (MFI). The samples were processed through density gradient centrifugation, and fluorescence-activated cell sorting to separate lymphoblasts and normal B-cells. RNA isolation, reverse transcribed into cDNA, and isoform-specific qPCR were performed.
Results:The expression intensity of sCD49f varied (range MFI: 3-9150). We determined both the intrapatient ratio of the isoforms and their relative quantity. Higher isoform B levels associated with higher sCD49f expression, while isoform A showed no correlation. Patients with over 10% measurable residual disease (MRD) at day 15 had significantly higher mRNA levels of both isoforms at diagnosis than those with lower MRD levels; sCD49f showed no correlation. Relapsed samples showed higher levels of both isoforms than diagnostic ones, while sCD49f expression remained stable. In samples with KMT2Ar (n=6), the ratio of A and B isoforms was significantly higher than in others, while sCD49f was lower in this genetic subgroup. In accordance with these findings in the ETV6::RUNX1 fusion group (n=12) A/B ratio was low, with higher sCD49f expression. Normal B-cells show no sCD49f expression, however both isoforms were detectable with high A/B ratio.
Conclusion: ITGA6B quantity correlates with sCD49f expression in B-lymphoblasts. Higher levels of both ITGA6A and ITGA6B predict an unfavorable prognosis as they associated with higher MRD rates. Furthermore, the quantity of both isoforms increased in relapsed samples. The A/B isoform ratio showed strong predictive value with a higher ratio indicating KMT2Ar and lower the presence of ETV6::RUNX1 fusion.
Funding: SE 250+ Excellence PhD Scholarship; 2025 Hungarian Pediatric Oncology Network