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Blood, Vol. 93 No. 11 (June 1), 1999:
pp. 3940-3948
Expression and Functional Characterization of the  -Isoform of the
Folate Receptor on CD34+ Cells
Joseph A. Reddy,
Laura S. Haneline,
Edward F. Srour,
Asok C. Antony,
D. Wade Clapp, and
Philip S. Low
From the Department of Chemistry, Purdue University, West Lafayette;
the Department of Pediatrics, Herman B. Wells Center for Pediatric
Research and the Department of Microbiology/Immunology, the Division of
Hematology-Oncology, the Department of Medicine, Indiana University
School of Medicine, Indianapolis; and the Roudebush Veterans Affairs
Medical Center, Indianapolis, IN.
We have investigated the expression and functional competence of
folate receptor (FR) isoforms on human hematopoietic cells. Using
immunofluorescence and reverse transcriptase-polymerase chain reaction
(RT-PCR) methodology, we find that a substantial fraction of
low-density mononuclear and CD34+ cells express both the
 and  isoforms of FR. The  isoform of FR (the form most
commonly found on cancer cells) was surprisingly absent from all
hematopoietic cells examined. Compared with KB cells (a human cell line
known for its elevated expression of FR-), the abundance of FR-
on CD34+ cell surfaces was relatively low ( 8% of KB
cell levels). Because many antifolates and folic acid-linked
chemotherapeutic agents enter malignant cells at least partially via FR
endocytosis, it was important to evaluate the ability of FR on
CD34+ cells to bind folic acid (FA). Based on three FR
binding assays, freshly isolated CD34+ cells were found
to display no affinity for FA. Thus, regardless of whether steps were
taken to remove endogenous folates before receptor binding assays, FR
on primitive hematopoietic cells failed to bind 3H-FA,
fluorescein isothiocyanate (FITC)-linked FA, or FA-derivatized liposomes. In contrast, analogous studies on KB cells showed high levels of receptor binding for all three FR probes. These studies show
that although multipotent hematopoietic progenitor cells express FR,
the receptor does not transport significant amounts of FA.
Consequently, antifolates and FA-linked chemotherapeutic agents that
can be engineered to enter malignant cells exclusively through the FR
should not harm progenitor/stem cell function.
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