Cortactin is Differentially Expressed in B‐cell Precursor Cells: Implications for Childhood Acute Lymphoblastic Leukemia

Abstract

Cortactin and HS1 are actin‐binding molecules known to be overexpressed in leukemic B‐cells from adult patients with chronic lymphoid leukemia. Both proteins are required for proper actin remodeling in virtually all cell types. While cortactin overexpression is associated to invasiveness of various solid tumor cells, HS1 is correlated with poor prognosis of chronic leukemia in adult patients. However, the role of cortactin and HS1 in childhood acute lymphoblastic leukemias (ALL) has never been studied. Here, we analyzed mRNA levels of both cortactin and HS1 in model cell lines for ALL and primary bone marrow (BM) cells from B‐ALL patients, and found substantial increases for both cortactin and HS1 in leukemic cells compared to controls. Furthermore, protein levels of cortactin were highest within primary primitive Lin‐CD34+ stem and progenitor cell compartments, while lineage committed CD34‐CD19+ and non‐B cells displayed low expression levels. By contrast, HS1 expression was high but did not change during differentiation. Unraveling the importance of differential expression of cortactin and HS1 in leukemia initiating cells for the population dynamics and development of childhood acute leukemias may open novel treatment strategies to prevent progression of the disease with infiltrations into other organs.