Folate receptor type β is a neutrophilic lineage marker and is differentially expressed in myeloid leukemia

BACKGROUND The membrane‐associated folate receptor (FR) type β is elevated in the spleen in patients with chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). In this study, the authors investigated possible cell type and differentiation stage specificity of expression of FR‐β in normal and leukemic hematopoietic cells. METHODS An affinity‐purified rabbit polyclonal antibody specific for FR‐β was employed for immunostaining representative bone marrow smears and peripheral blood smears from normal individuals and from a limited number of patients with various leukemias. Multiple samples of normal bone marrow and peripheral blood were analyzed for the expression of FR‐β and selected CD antigens by two‐ or three‐color flow cytometry. RESULTS Of the morphologically identifiable cells, only neutrophils were positive for FR‐β. The leukemic blasts in CML patients showed expression of FR‐β with no apparent relation to the occurrence of the Philadelphia chromosome. Among acute nonlymphocytic leukemias, FR‐β was expressed in promyelocytic leukemia, in the myeloblast populations of myelomonocytic and erythroleukemias, and variably in M1/M2 AML. Neither the blasts of acute lymphocytic leukemia nor the more mature cells of chronic lymphocytic and hairy cell leukemias expressed FR‐β. The less differentiated FR‐β positive AML samples also were positive for CD34 and HLA‐DR. Flow cytometric analysis of normal bone marrow and peripheral blood revealed low or insignificant coexpression of FR‐β with CD34, CD19, and CD3, whereas significant coexpression was observed with high levels of CD33, CD13, and CD11b; coexpression of FR‐β with CD14 was high in the immature bone marrow cells, comparable to that in myeloid cells, but relatively low in peripheral blood. CONCLUSIONS The results of this study suggest a narrow expression pattern of FR‐β marking the neutrophilic lineage and the possibility of defining a subtype or subtypes of myeloid leukemia based on FR‐β expression. The identification of FR‐β positive leukemias and the absence of the receptor in normal CD34 positive cells may enable selective receptor‐mediated targeting of leukemic cells. Cancer 1999;85:348–57. © 1999 American Cancer Society. In normal hematopoiesis, expression of folate receptor type β is highest in late stages of neutrophilic differentiation and insignificant in CD34+ cells. High expression of the protein is observed in certain myeloid leukemia cells, suggesting its potential usefulness as a pr