Heterogeneous expression of the collagen receptor DDR1 in chronic lymphocytic leukaemia and correlation with progression

Discoidin domain receptor (DDR)1 is a tyrosine kinase-receptor, which is activated by various types of collagens. 1 Several studies showed DDR1 expression in human cancers, and reported its role in cell proliferation, epithelial to mesenchymal transition, migration and invasiveness. 2 In addition, high DDR1 expression has been related to adverse prognosis in some human solid tumours. As far as haematological malignancies are concerned, DDR1 gene is highly expressed in adult B-ALL cases without ALL1/AF4 and E2A/PBX1 molecular rearrangements, as well as in B-cell receptor/ABL-positive cases. 3 Also, acute myeloid leukaemia (AML) blasts express DDR1, which provides a supportive stimulus in the bone marrow microenvironment. 4 Moreover, activation of DDR1 protects Hodgkin lymphoma cells from apoptosis. Although Hodgkin and Reed–Sternberg cells express DDR1, it is not detected in their normal counterpart, the germinal centre B cells of reactive tonsils. 5 The microenvironment of the bone marrow and secondary lymphoid organs has an essential role in chronic lymphocytic leukemia (CLL) pathogenesis and resistance to treatment. 6 Indeed, stimuli deriving from the B-cell receptor, cell-to-cell contacts with nurse-like cells or activated T cells, and several chemokines and cytokines promote CLL proliferation and survival. 6 , 7 In a previous study, we reported that IL-21, which regulates CLL B-cell survival in a context-dependent fashion, modulates the expression of several mRNAs, among which DDR1 was one of the most downregulated genes. 8 These data suggested that DDR1 may be expressed in CLL cells but, to the best of our knowledge, no other studies have specifically addressed this issue. Since CLL is a clinically heterogeneous disease, here we studied the expression of DDR1 gene in independent retrospective series of CLL in relationship to time to first treatment (TTFT), known prognostic markers, and miRNA expression.