IDENTIFICATION OF A NOVEL FOLATE RECEPTOR, A TRUNCATED RECEPTOR, AND RECEPTOR-TYPE-BETA IN HEMATOPOIETIC-CELLS - CDNA CLONING, EXPRESSION, IMMUNOREACTIVITY, AND TISSUE-SPECIFICITY

The expression of a membrane-associated folate receptor (FR) was eleva ted in spleen samples from patients with chronic (CML) and acute (AML) myelogenous leukemias compared with normal spleen. Contrary to earlie r reports, antibodies to a purified FR from placenta cross-reacted qua ntitatively with this protein in solution radioimmunoassays. Similar t o FR-alpha (KB cells) and FR-beta (placenta), the protein was released from the membrane by phosphatidylinositol-specific phospholipase C, i ndicating a glycosylphosphatidylinositol (GPI) membrane anchor. Screen ing of a cDNA library from CML spleen with a heterologous murine FR cD NA and also amplification of FR cDNAs from spleen and bone marrow in C ML, AML, chronic lymphocytic leukemia (CLL), and acute lymphocytic leu kemia (ALL) by polymerase chain reaction (PCR) using degenerate oligon ucleotides yielded cDNA clones representing FR-beta, a novel FR (type gamma), and an aberrant transcript of FR-gamma with a 2 base pair dele tion resulting in a truncated 104-residue polypeptide; FR-alpha was no t detected in these tissues. The cDNA for FR-gamma predicts a 243-resi due polypeptide with an amino acid sequence homology of 71% and 79% wi th FR-alpha and FR-beta, respectively, a 23-residue aminoterminal sign al peptide, and 3 potential sites for N-linked glycosylation. Transfec tion of COS-1 cells with the cDNA for FR-gamma resulted in low express ion of a [H-3]folic acid binding protein on the cell surface that was GPI-anchored. PCR analysis of total RNA from a number of normal and ma lignant tissues and cell lines indicated a limited tissue specificity of FR-gamma. FR-gamma and FR-beta could thus be potential differentiat ion markers in hematopoiesis and potential therapeutic targets in cert ain malignancies.