Expression of the hemoglobin scavenger receptor (CD163/HbSR) as immunophenotypic marker of monocytic lineage in acute myeloid leukemia

The hemoglobin-haptoglobin scavenger receptor (CD163/HbSR) is a monocyte/macrophage-restricted transmembrane protein of the scavenger receptor cysteine-rich family.1 Antigen expression is related to monocyte/macrophage differentiation, with weak expression on peripheral blood monocytes and abundant expression on the majority of tissue macrophages.2-4 To clarify2,3,5whether CD163/HbSR is also expressed on leukemic cells committed to the monocytic lineage, we measured cell-surface expression of CD163/HbSR on leukemic blast cells of 78 patients with acute myeloid leukemia (AML).

AML diagnosis was established by morphology and cytochemistry according to French-American-British (FAB) criteria and immunophenotyping.6 Cases were subclassified as M0 (n = 2), M1 (n = 9), M2, (n = 26), M3 (n = 5), M4 (n = 12), M5 (n = 19), M6 (n = 4), and M7 (n = 1). Density gradient–separated peripheral blood mononuclear cells were stained with fluorescein isothiocyanate (FITC)–labeled anti-CD163 antibody (clone 5C6-FAT; BMA Biomedicals, Augst, Switzerland) or an isotype control antibody (BD Biosciences, Heidelberg, Germany) for measurement of cell-surface CD163/HbSR expression by flow cytometry. Of 47 patients with AML subtypes other than M4 or M5, 41 (87%) had no or only minimal expression of CD163/HbSR (Figure1). In the remaining 6 patients, 5% to 8% of the leukemic blasts stained positively for the antigen when compared with the isotype control antibody. In none of the patients, however, did antigen expression exceed 8%. By comparison, 3 of 12 patients with AML M4 and 16 of 19 patients with AML M5 had CD163/HbSR expression 10% or higher (Figure 1). At the time of initial diagnosis, 2 patients with AML M5 were treated with glucocorticoids, drugs that are known to increase CD163/HbSR expression on normal macrophages;7their effect on antigen expression on malignant cells is, however, unknown.

In line with this lineage-restricted antigen expression, we observed strong correlations between CD163/HbSR and other markers predominantly found in monocytic leukemia,8,9 such as CD14, CD64, and lysozyme (Table1). Weaker correlations were found between CD163/HbSR and the myeloid markers CD15, CD33, CDw65, the percentage of unspecific esterase-positive blast cells, and transcobalamin II10(Table 1), but not for CD13 and CD117 (not shown). In addition, weak inverse correlations were found between CD163/HbSR expression and positivity of cytochemical staining for peroxidase and chloroacetate esterase and flow cytometric detection of intracellular myeloperoxidase (not shown), markers which are usually not expressed by monocytic leukemias.6 A weak correlation was also found for CD163/HbSR and blood levels of C-reactive protein, possibly reflecting the acute-phase regulated expression of CD163/HbSR.

In conclusion, these results confirm early studies2,3 and demonstrate that CD163/HbSR is expressed not only on mature monocytes and macrophages but also on leukemic cells. We found the antigen exclusively on the majority of monocytic and a significant subset of myelomonocytic leukemias, suggesting that the restriction of CD163/HbSR expression to cells committed to the monocytic lineage is preserved beyond malignant transformation; this lineage-restricted pattern of antigen expression may thus be useful for the immunophenotypic subclassification of leukemias.