AC133 항원 양성 급성백혈병의 생물학적 특성

Abstract

Background : AC133 antigen is a cell surface antigen which is selectively expressed on hematopoietc stem and progenitor cells. It has been reported that AC133 antigen is expressed on the subsets of CD34+ acute leukemia, and occasionally on CD34-acute leukemia. We investigated the clinical and biological characteristics of AC133 antigen-positive acute leukemia.

Method: Thirty-six adult acute leukemia patients were analyzed using a cut-off criterion of 20% or more gated leukemic blasts expressing the AC133 antigen for AC133+ leukemia. The biological characteristics focused on apoptosis were examined using multicolor flow cytometry and Western blot analysis.

Results: AC133 antigen was expressed in 12 cases (33.3%). Eleven of 21 (52.4%) acute myelogenous leukemia (AML) patients and 1 of 15 (6.7%) acute lymphoblastic leukemia patients were positive for AC133 antigen, and the difference was significant. None of the clinical prognostic markers were singificantly different between AC133+ and AC133- AML. Median disease free and overall survival time were not significantly different between AC133+ and AC133- AML. The expression rate of CD34 was significantly higher in AC133+ AML patients compared to those of AC133- AML (P=0.045). Among the apoptosis-related proteins, the Fas expression on the leukemic blasts was higher in the AC133+ AML(P=0.048), but Fas ligand, Bcl-2, caspase-3 expression rates were not significantly different between AC133+ and AC133 -AML. The apoptosis rate was signigicantly lower in the Ara-C treated AC133 + AML (P=0.049), but the apoptosis rates to other apoptosis-inducing agents (dox-orubicin, TNF-α) were not different between AC133+ and AC133-AML cells. We thought that there were some associations between a trend toward higher caspase-3 expression rates and lower Ara-C induced apoptosis rates in the AC133+ AML.

Conclusion : There was no significant correlation between AC133 antigen expression and various clinical characteristics of acute leukemia, but the AC133 antigen might provide different biological characteristics including apoptosis from other immature cell surface markers. However, to verify the prognostic usefulness of AC133 antigen and the basis of the biological characteristics of AC133 antigen-positive acute leukemia, further study is needed.