Imatinib mesylate affects extracellular ATP catabolism and expression of NTPDases in a chronic myeloid leukemia cell line

摘要: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, characterized by the occurrence of t(9;22)(q34;q11) translocation. First-line therapy for CML consists treatment with imatinib mesylate, which selectively inhibits BCR-ABL protein competing its ATP-binding site. Adenine nucleotide signaling modulated ectonucleotidases and this pathway related to tumorigenic processes. Considering relationship between ATP cancer, we aimed evaluate influence mesylate on expressions functions NTPDase ecto-5′-nucleotidase (CD73) enzymes in imatinib-sensitive -resistant K-562 cell lines. mRNA analysis showed that cells express all ENTPDs NT5E. However, when treated 24 h, expression ENTPD1, -2, -3 -5 increased, leading higher nucleotides hydrolysis rate. HPLC identified increased degradation after 24 h treatment, consequent ADP AMP formation, corroborating increase gene as observed previous results. On other hand, imatinib-resistant presented decrease ENTPD1 -5. These results suggest an involvement modulating will need further investigation. Since these have important catalytic activities tumor microenvironment, their modulation may represent therapeutic approach regulate levels extracellular adenine nucleotides.