ORIGINAL PAPER HLA-G expression in acute lymphoblastic leukemia: a significant prognostic tumor biomarker Noura Alkhouly • Iman Shehata • Manal Basyouni Ahmed • Hanan Shehata • Sara Hassan • Tamer Ibrahim Received: 21 October 2012 / Accepted: 7 January 2013 Ó Springer Science+Business Media New York 2013 Abstract Human leukocyte antigen G (HLA-G) is a non- classical major histocompatibility class Ib antigen with multiple immune regulatory functions including the induc- tion 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 mono- nuclear 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-c, and with natural killer (NK) cells. Serum levels of IL-10 and INF-c 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-c 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-c. The positive correlation of membrane HLA-G expression with both IL-10 and INF-c 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. Keywords Acute lymphoblastic leukemia Á HLA-G Á IL-10 Á INF-c Á NK cells Introduction Acute lymphoblastic leukemia (ALL) is a heterogeneous disease, both in terms of its pathology and the populations that it affects. Although ALL is a success story in pediatric oncology, results in adults lag behind those in children [1]. Acute leukemias are usually rapidly progressive with death often occurring in a few weeks to a few months in untreated patients as a result of abnormal hematopoietic function as well as impaired immune response [2]. There is a strong circumstantial evidence that the tumor growth can be actively controlled by the host immune system. Tumor escape from host immune surveillance is N. Alkhouly Á M. B. Ahmed (&) Á H. Shehata Medical Biochemistry, Faculty of Medicine, Ain Shams University, Abbasia, Cairo, Egypt e-mail: manal_basiony@yahoo.com I. Shehata Medical Microbiology and Immunology, Faculty of Medicine, Ain Shams University, Abbasia, Cairo, Egypt S. Hassan Clinical Pathology, Faculty of Medicine, Ain Shams University, Abbasia, Cairo, Egypt T. Ibrahim Internal Medicine (Hematology Department), Faculty of Medicine, Ain Shams University, Abbasia, Cairo, Egypt 123 Med Oncol (2013) 30:460 DOI 10.1007/s12032-013-0460-8