WT1 expression in peripheral leukocytes of patients with chronic myeloid leukemia serves for the prediction of Imatinib resistance.
The determination of patient's resistance to a particular drug contributes to more efficient therapeutical approach. The aim of this study was to evaluate if the responsiveness of Chronic Myeloid Leukemia (CML) patients to Imatinib therapy was predictable from WT1 gene expression in peripheral blood leukocytes. To examine the resistance we implemented an in vitro cultivation of the primary cells of 48 CML patients with Imatinib. The effect of Imatinib was characterized not only by the expression of WT1 but also by BCR-ABL, and proliferative factor Ki-67. <br />Our results showed that leukocytes of CML patients, clinically responsive to Imatinib treatment, significantly decreased WT1 expression after in vitro incubation with Imatinib. It was accompanied by an inhibition of expression of Ki-67 but not BCR-ABL. In leukocytes of CML patients clinically resistant to Imatinib, the expression of WT1, Ki-67, and BCR-ABL remained unaffected. The presented results showed that in vitro testing using peripheral blood cells enabled clinicians to predict responsiveness of CML patients to Imatinib.
Otahalova
E
E
Department of Molecular Genetics, Institute of Hematology and Blood Transfusion, U Nemocnice 1, Czech Republic.
Ullmannova-Benson
V
V
Klamova
H
H
Haskovec
C
C
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D019394:Ki-67 Antigen / Q000235:genetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D025721:WT1 Proteins / Q000235:genetics*
D000970:Antineoplastic Agents; D001549:Benzamides; D019394:Ki-67 Antigen; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D025721:WT1 Proteins; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl