Unfavorable clinical implications for HLA-G expression in acute myeloid leukemia.
Medical Research Center, Taizhou Hospital of Zhejiang province, Wenzhou Medical College, Linhai, Zhejiang 317000, People's Republic of China. Journal of Cellular and Molecular Medicine
(Impact Factor: 4.01).
12/2007; 12(3). DOI: 10.1111/j.1582-4934.2007.00175.x
Human leukocyte antigen-G (HLA-G) molecule exerts multiple immunoregulatory functions which have been suggested to contribute to the immune evasion of tumor cells. Studies on HLA-G expression in malignant hematopoietic diseases are controversial and the functions of HLA-G on this context are limited. In the current study, HLA-G expression was analyzed in different types of patients: de novo acute myeloid leukemia (AML, n=54), B cell acute lymphoblastic leukemia (B-ALL, n=13), chronic myeloid leukemia (CML, n=9) and myelodysplastic syndrome (MDS, n=11). HLA-G expression was observed in 18.5% cases of AML, 22.2% in CML and 18.2% in MDS, but not in B-ALL patients. In AML, HLA-G-positive patients had a significant higher bone marrow leukemic blast cell percentage when compared with that of HLA-G negative patients (p<0.01). Total T cell percentage was dramatically decreased in HLA-G positive patients (p<0.05). Cytogenetic karyotyping results showed that all HLA-G positive AML patients (n=5) were cytogenetically abnormal which was markedly different from that of HLA-G negative patients (p<0.01). ex vivo cytotoxicity analysis revealed that HLA-G expression in AML leukemic cells could directly inhibit NK cell cytolysis (p<0.01). These findings indicated that HLA-G expression in AML is of unfavorable clinical implications, and that HLA-G could be a potential target for therapy.
Available from: Joel Lemaoult
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ABSTRACT: Human leukocyte antigen G (HLA-G) is a nonclassic major histocompatibility complex (MHC) class I molecule that functions as an immunomodulatory molecule capable of protecting fetal tissues from the maternal immune system. The relevance of HLA-G in other contexts was investigated soon afterward. Numerous studies have sought (and some have shown) the relevance of HLA-G in pathologic conditions, such as transplantation, autoimmunity, and cancer and hematologic malignancies. One of the main goals of the current research on HLA-G is now to use it in the clinic, either for diagnosis or as a therapeutic tool/target. For this, precise knowledge on the nature and functions of HLA-G is critical. We highlight here what we consider are recent key basic findings on the immunomodulatory function of HLA-G. These strengthen the case for considering HLA-G as clinically relevant.
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ABSTRACT: 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.
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