Phosphoinositide-3-Kinase Plays a Vital Role in Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cells Transplantation

Abstract

Phosphoinositide-3 kinase (PI3K) plays a vital role in T-cell signaling pathway including cell proliferation, differentiation, migration and so on. Scholars have found that PI3K expression is limited to cells related with transplant rejection activation of the immune cells. PI3K plays a crucial role in GVHD occurrence: 1 crucial, PI3K are located in main areas in T-cell activation signal, resulting in affecting GVHD significantly; 2 selective, PI3K expression is limited to the participation of activated cells with immune rejection. But the expression of PI3K in GVHD patients has been not clear. In order to give the more experimental evidence for prophylaxis and treatment of GVHD, PI3K gene expression in patients with different state of GVHD was detected. This research collected the peripheral blood lymphocytes in 32 patients after allogeneic hematopoietic stem cell transplantation from January 2007 to January 2008. The cases include 15 male and 17 female cases, the median age was 27.9 (14–43) years. In accord with the classification of GVHD, all cases were divided into ALL (12), AML (7), CML (10), CMML (2), MDS (1). After one year after transplantation, the number of patients with no-GVHD is 9, simply aGVHD is 8, single-cGVHD is 8, aGVHD and cGVHD is 7. The total sample number is 122(state of blood reconstruction 32, no GVHD 37, aGVHD 27, cGVHD 26). By real-time PCR, PI3K expression were determined of patients at normal blood reconstruction, and at the 30th day, the 60th day, the 90th day, the 180th day, the 270th day, the 360th day after allogeneic hematopoietic stem cell transplantation. Matching with own blood reconstruction, PI3K expression in acute or chronic GVHD patients is statistical difference significantly. At the state of No-GVHD, aGVHD and cGVHD, it was 2.51 ± 1.16, 7.15 ± 5.92, 4.35 ± 3.14 respectively. Results suggest that, comparing with no-GVHD, PI3K expression with aGVHD increase significantly. And PI3K expression increase significantly when occuring cGVHD, but it is less than with aGVHD. In the experiment we also found, PI3K expressed in lymphocytes correlated with the increasing degree of GVHD. Particularly in the cGVHD, PI3K expression increased significantly when GVHD becoming more serious; with access to stable cGVHD, PI3K expression gradually become flat. We can draw the conclusions from this study: PI3K gene expression increased significantly in patients with GVHD than that of patients with no-GVHD, and related to different stages of GVHD. PI3K expression increased in cGVHD patients than that of patients with normal hematopoietic reconstruction, but the amplitude is not significant than that of aGVHD.