Molecular recognition of acute myeloid leukemia using aptamers.
Cell surface proteins can play important roles in cancer pathogenesis. Comprehensive understanding of the surface protein expression patterns of tumor cells and, consequently, the pathogenesis of tumor cells depends on molecular probes against these proteins. To be used effectively for tumor diagnosis, classification and therapy, such probes would be capable of specific binding to targeted tumor cells. Molecular aptamers, designer DNA-RNA probes, can address this challenge by recognizing proteins, peptides and other small molecules with high affinity and specificity. Through a process known as cell-based SELEX, we used live acute myeloid leukemia (AML) cells to select a group of DNA aptamers, which can recognize AML cells with dissociation constants (Kd's) in the nanomolar range. Interestingly, one aptamer (KH1C12) compared with two control cell lines (K562 and NB4) showed significant selectivity to the target AML cell line (HL60) and could recognize the target cells within a complex mixture of normal bone marrow aspirates. The other two aptamers KK1B10 and KK1D04 recognize targets associated with monocytic differentiation. Our studies show that the selected aptamers can be used as a molecular tool for further understanding surface protein expression patterns on tumor cells and thus providing a foundation for effective molecular analysis of leukemia and its subcategories.
Sefah
K
K
Department of Chemistry, Center for Research at Bio/nano Interface, University of Florida, Gainesville, FL 32611-7200, USA.
Tang
Z W
ZW
Shangguan
D H
DH
Chen
H
H
Lopez-Colon
D
D
Li
Y
Y
Parekh
P
P
Martin
J
J
Meng
L
L
Phillips
J A
JA
Kim
Y M
YM
Tan
W H
WH
D000951:Antigens, Neoplasm / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism; D052157:Aptamers, Nucleotide / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000473:pathology; D015336:Molecular Probe Techniques; D011485:Protein Binding; D052156:SELEX Aptamer Technique; D012680:Sensitivity and Specificity
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D052157:Aptamers, Nucleotide