Human leukocyte antigen G (
HLA-G) is a non-classical major histocompatibility class Ib
antigen with multiple immune regulatory functions including the induction of immune tolerance in
malignancies. The goal of our study was to investigate the expression of membrane form of
HLA-G in
acute lymphoblastic leukemia (ALL) before and after
therapy in a trial to evaluate its role as a tumor escape mechanism and prognosis. So we measured its expression by reverse transcription (RT)-PCR in peripheral blood mononuclear cells of 25 (ALL) patients and 15 healthy controls and correlated our findings with a variety of clinical and laboratory variables and two important
cytokines,
IL-10 and INF-γ, and with natural killer (NK) cells. Serum levels of
IL-10 and INF-γ were measured by ELISA. NK cells were quantitated by flow cytometry. The best cutoff values for the investigated markers were determined by ROC curve. The current study showed that membrane-bound
HLA-G expression levels and positivity rates above the cutoff value 0.37 were significantly higher in ALL patients at diagnosis compared to after
therapy and both showed significant higher levels than in normal control group (P < 0.01). Moreover,
IL-10 and INF-γ serum levels were significantly elevated in ALL patients at time of diagnosis compared to healthy controls with a significant reduction in their levels in ALL patients after receiving
chemotherapy. Membrane
HLA-G expression showed a significant positive correlation with
lactate dehydrogenase, peripheral and bone marrow blast cells and with
IL-10 and INF-γ. The positive correlation of membrane
HLA-G expression with both
IL-10 and INF-γ serum levels supports the speculation that both
cytokines may be involved in the control of
HLA-G expression.
HLA-G showed a negative correlation with NK cells confirming its importance in tumor escape through down-regulation of NK cells. In conclusion,
HLA-G expression could be used as a prognostic
tumor marker to monitor disease state and improvement in ALL.