Abstract
Human leukocyte antigen-class I (HLA-I) molecules are membrane-associated proteins that contain two separate polypeptide chains: an alpha heavy chain and a beta chain. The beta chain is the b-2 microglobulin (b2-M). Significant levels of free soluble HLA-I (sHLA-I) have been detected in serum and studied as a marker for immunomodulation in patients with infection and after transplant. Little is known about the role of sHLA-I as a tumor marker, despite the documentation of b2-M as a tumor marker. We measured the levels of sHLA-I and b2-M in the plasma of 205 patients with acute myeloid leukemia (AML) and 95 patients with myelodysplastic syndrome (MDS) and assessed the value of both markers in predicting clinical behavior. Both sHLA-I and b2-M were strong predictors of response to therapy (P = 0.03 and P = 0.001, respectively), overall survival (both P <0.0001), and remission duration (both P <0.001). The Multivariate Cox proportional hazards model incorporating cytogenetics, b2-M, and sHLA-I demonstrated that only b2-M was an independent predictor of survival. In patients with MDS, b2-M but not sHLA-I correlated with response to therapy, overall survival, and response duration. These data not only establish the role of sHLA-I as a tumor marker in AML, but also suggest that MDS disease is significantly different from AML. Because sHLA-I has been reported to be an immunomodulator that inhibits the cytotoxic effects of T-lymphocytes, its role as an immunomodulator in patients with MDS needs further investigation.
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