SUMMARY Growth and maturation of B lymphocytes from stem cells require a series of complex processes that are dependent at least in part on growth factors. Uncontrolled expression of receptors from these early growth factors may contribute to a leukaemogenesis of such early B cell progenitors. We show here that early pre-pre-B cells, but not mature B cells, express the PDGF receptor-beta (PDGFR-β). These receptors contain a protein tyrosine kinase domain which is activated upon ligation with PDGF in pre-pre-B cells. Further, pre-pre-B leukaemia cells seem to express more PDGFR-β compared with their normal counterparts, suggesting a role for these receptors in growth promotion of leukaemia cells.
B cell receptor (BCR)-signaling inhibitors such as Ibrutinib and Idelalisib do not cure CLL, suggesting the importance of other pathways.1 Cytokines are also important in CLL biology and mediate transcription of oncogenic genes such as miR-17 by activating signal transducer and activator of transcription (STAT) proteins including STAT5A/B and STAT3 through Janus kinases (JAKs).2–4 We hypothesized that Ruxolitinib, a selective JAK1/2 inhibitor licensed for myelofibrosis,5 might have unrecognized activity in CLL and designed a single center phase II trial to evaluate it in patients considered unfit for FCR on the basis of age and comorbidities.6 The demonstrated safety of Ruxolitinib in myelofibrosis was felt to make it ethical to use as first-line therapy for elderly CLL patients. The primary endpoint was overall response rate (ORR) assessed after 7 treatment cycles.7 Secondary endpoints were safety and tolerability.7 The study was approved by the Sunnybrook REB and Health Canada and registered with ClinicalTrials.gov, {type:clinical-trial,attrs:{text:NCT02015208,term_id:NCT02015208}}NCT02015208.
