TY - JOUR
T1 - Expression of the nucleoside transporters hENT1 (SLC29) and hCNT1 (SLC28) in pediatric acute myeloid leukemia
AU - Jaramillo, Adrian Christopher
AU - Hubeek, Isabelle
AU - Broekhuizen, Richard
AU - Pastor-Anglada, Marçal
AU - Kaspers, Gertjan J.L.
AU - Jansen, Gerrit
AU - Cloos, Jacqueline
AU - Peters, Godefridus J.
PY - 2020
Y1 - 2020
N2 - Cellular uptake of clinically important deoxynucleoside analogs is mediated by nucleoside transporters including the human equilibrative nucleoside transporter 1 (hENT1) and the concentrative nucleoside transporter-1 (hCNT1). These transporters are responsible for influx of cytarabine and reduced hENT1 expression is a major resistance mechanism in acute myeloid leukemia. We determined hENT1 and hCNT1 protein expression by immunocytochemistry in 50 diagnostic pediatric acute myeloid leukemia patient samples. All samples expressed hENT1 [9/43 (21%) low; 26/43 (60%) medium and 8/43 (19%) high] and hCNT1 [2/42 (5%) low; 35/42 (83%) medium and 5/42 (12%) high] at the cell membrane and cytoplasm. Statistical analysis showed a non-significant relationship between survival and transporter expression and in vitro drug sensitivity. In conclusion, the nucleoside transporters hENT1 and hCNT1 are broadly expressed in pediatric acute myeloid leukemia at diagnosis.
AB - Cellular uptake of clinically important deoxynucleoside analogs is mediated by nucleoside transporters including the human equilibrative nucleoside transporter 1 (hENT1) and the concentrative nucleoside transporter-1 (hCNT1). These transporters are responsible for influx of cytarabine and reduced hENT1 expression is a major resistance mechanism in acute myeloid leukemia. We determined hENT1 and hCNT1 protein expression by immunocytochemistry in 50 diagnostic pediatric acute myeloid leukemia patient samples. All samples expressed hENT1 [9/43 (21%) low; 26/43 (60%) medium and 8/43 (19%) high] and hCNT1 [2/42 (5%) low; 35/42 (83%) medium and 5/42 (12%) high] at the cell membrane and cytoplasm. Statistical analysis showed a non-significant relationship between survival and transporter expression and in vitro drug sensitivity. In conclusion, the nucleoside transporters hENT1 and hCNT1 are broadly expressed in pediatric acute myeloid leukemia at diagnosis.
KW - Acute myeloid leukemia (AML)
KW - acute lymphoblastic leukemia (ALL)
KW - bovine serum albumin (BSA)
KW - cytarabine (Ara-C)
KW - deoxynucleoside analogs (NAs)
KW - human concentrative nucleoside transporter-1 (hCNT1)
KW - human equilibrative nucleoside transporter-1 (hENT1)
KW - phosphate buffered saline (PBS)
UR - http://www.scopus.com/inward/record.url?scp=85083716829&partnerID=8YFLogxK
U2 - https://doi.org/10.1080/15257770.2020.1746803
DO - https://doi.org/10.1080/15257770.2020.1746803
M3 - Article
C2 - 32312148
SN - 1525-7770
VL - 39
SP - 1379
EP - 1388
JO - Nucleosides, Nucleotides and Nucleic Acids
JF - Nucleosides, Nucleotides and Nucleic Acids
IS - 10-12
ER -