BACKGROUND: The membrane-associated folate receptor (FR) type beta 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-beta in normal and leukemic hematopoietic cells. METHODS: An affinity-purified rabbit polyclonal antibody specific for FR-beta 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-beta and selected CD antigens by two- or three-color flow cytometry. RESULTS: Of the morphologically identifiable cells, only neutrophils were positive for FR-beta. The leukemic blasts in CML patients showed expression of FR-beta with no apparent relation to the occurrence of the Philadelphia chromosome. Among acute nonlymphocytic leukemias, FR-beta 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-beta. The less differentiated FR-beta 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-beta with CD34, CD19, and CD3, whereas significant coexpression was observed with high levels of CD33, CD13, and CD11b; coexpression of FR-beta 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-beta marking the neutrophilic lineage and the possibility of defining a subtype or subtypes of myeloid leukemia based on FR-beta expression. The identification of FR-beta positive leukemias and the absence of the receptor in normal CD34 positive cells may enable selective receptor-mediated targeting of leukemic cells.
BACKGROUND: The membrane-associated folate receptor (FR) type beta 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-beta in normal and leukemic hematopoietic cells. METHODS: An affinity-purified rabbit polyclonal antibody specific for FR-beta 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-beta and selected CD antigens by two- or three-color flow cytometry. RESULTS: Of the morphologically identifiable cells, only neutrophils were positive for FR-beta. The leukemic blasts in CMLpatients showed expression of FR-beta with no apparent relation to the occurrence of the Philadelphia chromosome. Among acute nonlymphocytic leukemias, FR-beta 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-beta. The less differentiated FR-beta 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-beta with CD34, CD19, and CD3, whereas significant coexpression was observed with high levels of CD33, CD13, and CD11b; coexpression of FR-beta 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-beta marking the neutrophilic lineage and the possibility of defining a subtype or subtypes of myeloid leukemia based on FR-beta expression. The identification of FR-beta positive leukemias and the absence of the receptor in normal CD34 positive cells may enable selective receptor-mediated targeting of leukemic cells.
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Authors: Michael Heuser; Bennet Heida; Konstantin Büttner; Clara Philine Wienecke; Katrin Teich; Carolin Funke; Maximilian Brandes; Piroska Klement; Alessandro Liebich; Martin Wichmann; Blerina Neziri; Anuhar Chaturvedi; Arnold Kloos; Konstantinos Mintzas; Verena I Gaidzik; Peter Paschka; Lars Bullinger; Walter Fiedler; Albert Heim; Wolfram Puppe; Jürgen Krauter; Konstanze Döhner; Hartmut Döhner; Arnold Ganser; Michael Stadler; Lothar Hambach; Razif Gabdoulline; Felicitas Thol Journal: Blood Adv Date: 2021-05-11