Expression of interferon regulatory factor 4 in chronic myeloid leukemia: Correlation with response to interferon alfa therapy

Purpose: Mice experiments have established an important role for interferon regulatory factor (IRF) family members in hematopoiesis. We wanted to stud y the expression of interferon regulatory factor 4 (IRF4) in various hemato logic disorders, especially chronic myeloid leukemia (CML), and its associa tion with response to interferon alfa (IFN-alpha) treatment in CML. Materials and Methods: Blood samples from various hematopoietic cell lines, different leukemia patients (70 CML, 29 acute myeloid leukemia [AML], 10 c hronic myelomonocytic leukemia [CMMoL], 10 acute lymphoblastic leukemia, an d 10 chronic lymphoid leukemia patients), and 33 healthy volunteers were mo nitored for IRF4 expression by reverse transcriptase polymerase chain react ion. Then, with a focus on CML, the IRF4 level was determined in sorted cel l subpopulations from CML patients and healthy volunteers and in in vitro-s timulated CML cells. Furthermore, IRF4 expression was compared in the CML s amples taken before IFN-alpha therapy and in 47 additional CML samples take n during IFN-alpha therapy, IRF4 expression was then correlated with cytoge netic response to IFN-alpha. Results: IRF4 expression wets significantly impaired in CML, AML, and CMMoL samples. The downregulation of IRF4 in CML samples was predominantly found in T cells. In CML patients during IFN-alpha therapy, a significant increa se in IRF4 levels wets detected, and this was also observed in sorted T cel ls from CML patients. The increase seen during IFN-alpha therapy wets not d ue to different blood counts. In regard ta the cytogenetic response with IF N-alpha, a good response wets associated with high IRF4 expression. Conclusion: IRF4 expression is downregulated in T cells of CML patients, an d its increase is associated with a good response to IFN-alpha therapy. The se data suggest IRF4 expression as a useful marker to monitor, if not predi ct, response to IFN-alpha in CML, J Clin Oncol 18:333]-3338, (C) 2000 by Am erican Society of Clinical Oncology.