The kinetics of mRNA transforming growth factor beta1 expression and its serum concentration in graft-versus-host disease after allogeneic hemopoietic stem cell transplantation for myeloid leukemias

Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland.
Medical science monitor: international medical journal of experimental and clinical research (Impact Factor: 1.43). 06/2011; 17(6):CR322-8. DOI: 10.12659/MSM.881804
Source: PubMed


Graft-versus-host disease (GVHD) is still a major complication following allogeneic hematopoietic stem cell transplantation (alloHSCT). Recent data indicates that transforming growth factor beta1 (TGF-beta1) may play a role in development of GVH reaction.
Forty patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) were included. Quantitative real time polymerase chain reaction (RT-qPCR) was performed to assess the expression of mRNA TGF-beta1. TGF-beta1 serum concentration was assessed using a commercial ELISA.
In all patients, a prompt decrease in TGF-beta1 mRNA expression and its serum concentration was demonstrated after conditioning. In patients with acute GVHD, TGF-beta1 mRNA expression and its serum concentration remained low until day +30 after transplant as compared to the day of transplant (p<0.03 and p<0.006, respectively). TGF-beta1 mRNA expression and its serum concentration significantly increased on day +100 in patients who developed chronic GVHD as compared to the day of transplant (p<0.0009 and p<0.02, respectively).
TGF-beta1 seems to be an additional regulator of donor engraftment; its low levels probably being one of the factors contributing to the development of acute GVHD. On the other hand, chronic GVHD symptoms seem to correlate with high TGF-beta1 mRNA expression and its serum concentration in patients who underwent bone marrow transplantation for myeloid leukemias. Nevertheless, further studies with greater numbers of patients are needed to establish the role of TGF-beta1 in graft-versus-host disease pathophysiology.

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    ABSTRACT: Hematopoietic stem cell transplantation (HSCT) is a medical procedure used to treat malignant and nonmalignant haematological diseases, congenital immunodeficiency syndromes, solid tumours and metabolic diseases. Despite its usefulness, several major complications, such as graft-versus-host disease, can negatively affect patients treated with HSCT. Apart from clinical factors well known to affect the outcome of HSCT, patient and donor genetics have been shown to play an important role in the susceptibility to post-transplant complications. Histocompatibility as determined by the human leucocyte antigen (HLA) system has been a major genetic determinant of the success of HSCT. Non-HLA immunogenetics are increasingly recognized to play a part in the events related to transplantation. Cytokine genes, and their receptors, bear a considerable amount of polymorphism. One of the genes that may play an important role on the outcome of allogeneic HSCT is TGFB1, which encodes transforming growth factor, betaeta 1 (TGF-beta1). TGF-beta1 is a pleiotropic cytokine, which plays a central role in the development, homeostasis and responses of the immune system. Several functional polymorphisms in TGFB1 have been identified, and these are known to cause alterations in cytokine secretion in several settings. The present review will focus on the current knowledge surrounding the effect of polymorphisms within TGFB1 on the outcome of HSCT.
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    ABSTRACT: Transforming growth factor (TGF)-β is a pleiotropic cytokine with widespread and profound effects on immune cells. Consequently, it has generated considerable interest in relation to the immunologic outcomes after allogeneic hematopoietic cell transplantation. The TGF-β pathway has been shown to be an important modulator of alloimmunity, with direct consequences on graft-versus-host disease pathophysiology and graft-versus-tumor response. The TGF-β-related effects can be both beneficial and detrimental to the host, underscoring the complexity of TGF-β biology. This article reviews the evidence linking TGF-β to alloimmune responses in allogeneic hematopoietic cell transplantation and highlights foreseeable strategies that would maximize the beneficial effects of TGF-β pathway modulation on both graft-versus-host disease pathophysiology and the graft-versus-tumor effect.
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