[Investigation of CD49f expression in childhood and adult B-cell acute lymphoblastic leukemia].
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INTRODUCTION: B-cell acute lymphoblastic leukemia is one of the most common malignancies in children, but it is rare in adults. Based on our previous findings in pediatric patients, CD49f integrin was expressed on lymphoblasts in most cases and its intense expression at diagnosis was associated with the ETV6::RUNX1 fusion. OBJECTIVE: Adult-onset B-cell acute lymphoblastic leukemia is characterized by a poor prognosis, therefore investigating the background and mechanisms of the disease is an important task. Our goal was to determine CD49f expression at diagnosis and during treatment, and to compare it with the genetic background and clinical data of patients. We also planned to determine the activity of signal transduction pathways originating from CD49f. METHOD: We examined CD49f expression by flow cytometry in bone marrow samples from children (n = 84) and adults (n = 24) with B-cell acute lymphoblastic leukemia, and examined the signaling molecules activated by CD49f by immunohistochemistry in bone biopsies (n = 10). We compared clinical and genetic data with expression. RESULTS: CD49f was detectable in 92% of diagnostic bone marrow samples from children and in 75% of samples from adult patients. We observed a significant increase in CD49f expression in samples from children with measurable residual disease, but no change in adults. In children, more intense CD49f expression at diagnosis predicted a higher rate of measurable residual disease, while in adults it correlated with weaker expression at diagnosis. In terms of genetic groups, we found more intense CD49f expression in the group with a better prognosis and reduced expression in lesions with a poor prognosis (KMT2A gene rearrangement) (P<0.001). When examining signaling pathways, intense CD49f expression was associated with increased Src and focal adhesion kinase staining, while integrin-linked kinase activation was not observed. DISCUSSION: CD49f proved to be a reliable measurable residual disease marker in both populations. In children, CD49f expression intensity at diagnosis was higher in patients belonging to the high-risk group than in those belonging to the low-risk group. In contrast, in adults, we observed weaker expression initially in measurable residual disease-positive patients. We found similar correlations between genetic groups and CD49f intensity values in pediatric and adult patient populations. CD49f expression was correlated with increased focal adhesion kinase-Src signaling activity. CONCLUSION: Based on our results, the CD49f molecule can be used as a measurable residual disease marker in both pediatric and adult B-cell acute lymphoblastic leukemia patient groups, and its expression correlates with genetic abnormalities and focal adhesion kinase-Src pathway activation. Orv Hetil. 2025; 166(50): 1983-1992.