Dysregulated Expression of CD28 and CTLA-4 Molecules in Patients with Acute Myeloid Leukemia and Possible Association with Development of Graft versus Host Disease after Hematopoietic Stem Cell Transplantation

Abstract

Background: Dysregulated expression of co-stimulatory molecules is one of the immune escape mechanisms employed in hematologic malignancies like acute myeloid leukemia (AML).

Objective: To evaluate the expression of the CD28 and CTLA-4 molecules in 62 adults with de novo AML and its correlation with the development of acute graft vs host disease (GVHD) after hematopoietic stem-cell transplantation.

Methods: The relative expression of CD28 and CTLA-4 was measured by quantitative SYBR Green real-time PCR method in a group of patients and controls as well as different risk groups (high, intermediate and favorite risk), M3 vs non-M3 and GVHD vs non-GVHD patients.

Results: The mRNA expression of CD28 (7.9-fold) and CTLA-4 (5.7-fold) was significantly increased in AML patients compared with healthy controls (p=0.006 and 0.02, respectively). Although the mean expression of both CD28 and CTLA-4 was increased in high-risk group compared with low-risk and intermediate- risk groups, the difference was not statistically significant. Also, the mean expression of the CTLA-4, but not CD28, was significantly higher in M3 patients compared with non-M3 ones (p<0.001). The expression of CD28 was upregulated in GVHD patients, while the expression of CTLA-4 was slightly lower in GVHD patients compared with non-GVHD patients, though the difference was not statistically significant. There was no significant correlation between the expression of CD28 and CTLA-4 and laboratory parameters like white blood cells and platelets counts, and hemoglobin and lactate dehydrogenase level in AML patients.

Conclusion: CD28 and CTLA-4 molecules are aberrantly expressed in peripheral blood leukocytes of AML patients and might contribute to the development of aGVHD after hematopoietic stem cell transplantation.