Decreased expression of CXCR4 chemokine receptor in bone marrow after chemotherapy in patients with non-Hodgkin lymphomas is a good prognostic factor

Abstract

Background: CXCR4 chemokine receptor is constitutively expressed on normal and malignant B lymphocytes derived from patients with B-cell lymphoproliferative disorders and has a significant role in cell migration to lymph nodes and bone marrow. Non-Hodgkin's lymphomas (NHL) constitute a heterogeneous group of lymphoproliferative diseases, which can localize not only to lymph nodes, but also can migrate to peripheral blood and metastase to other organs, including bone marrow. Aim: The purpose of this study was to determine CXCR4 gene expression in peripheral blood and bone marrow of NHL patients before and after treatment. Methods: Samples of lymphoma lymph nodes, peripheral blood and bone marrow aspirates of patients with B-cell NHL were taken at diagnosis and after chemotherapy. Gene expression was determined by the reverse transcription (RT)-polymerase chain reaction method. Expression was estimated from 0 AU (no amplificate signal) to 3 AU (maximal amplificate signal). Results: No significant difference in the level of CXCR4 expression was found in reactive lymph nodes compared to lymphoma samples We observed high level of CXCR4 expression in most patients before treatment: in bone marrow: 3 AU-10 pts, 2 AU-8 pts, 1 AU-2 pts. In peripheral blood: 3 AU-14 pts, 2 AU-4 pts, 1 AU-1 pts, 0 AU-1 pts. After chemotherapy, significant decrease in CXCR4 expression was observed. Bone marrow: 3 AU-5 pts, 2 AU-7 pts, 1 AU-5 pts, 0 AU-3 pts (p = 0.03). Peripheral blood: 3 AU-2 pts, 2 AU-6 pts, 1 AU-10 pts, 0 AU-2 pts (p = 0.0002). There was a good response to treatment in patients with significant decrease of CXCR4 expression in the bone marrow after treatment with 10-fold lower risk of death (p = 0.03). Conclusions: Decrease in CXCR4 expression in the bone marrow of NHL patients after chemotherapy may be a good prognostic factor. © 2014 Mazur et al.