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

M Ramzi, M Iravani Saadi, R Yaghobi, N Arandi

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.


Keywords


Acute graft versus host disease (aGVHD); AML; Co-stimulatory molecules; Hematopoietic stem cell transplantation (HSCT)

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 pISSN: 2008-6489
 eISSN: 2008-6490