Role of hTERT and WT1 gene expression in disease progression and imatinib responsiveness of patients with BCR-ABL positive chronic myeloid leukemia

Leuk Lymphoma. 2011 Apr;52(4):687-93. doi: 10.3109/10428194.2010.550978. Epub 2011 Feb 14.

Abstract

Most cases of leukemia show hTERT and WT1 gene overexpression. However, the role of these genes in the progression and monitoring of chronic myeloid leukemia (CML) has not been very well explored. Two hundred and eight patients diagnosed as having CML in chronic phase (CP), accelerated phase (AP), and blast crisis (BC) were studied. Real-time polymerase chain reaction (PCR) was performed for comparative quantification of BCR-ABL, hTERT, and WT1 gene expression. The expression levels of the three genes were compared among the three phases and seven imatinib-naive and -treated subgroups. Among the three major groups, the gene expression levels of hTERT (p < 0.01) and WT1 (p < 0.01) were significantly different. Freshly diagnosed, imatinib-responsive, and -unresponsive patients among these revealed interesting changes in hTERT and WT1 gene expression profiles, especially in 25 patients with CML in whom sequential samples were analyzed. Our results showed that hTERT and WT1 gene expression analyses provided relevant information for the understanding of disease progression and indicate their possible usefulness as surrogate markers for treatment monitoring.

MeSH terms

  • Benzamides
  • Disease Progression
  • Fusion Proteins, bcr-abl / genetics*
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Neoplasm Staging
  • Piperazines / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Telomerase / genetics
  • Telomerase / metabolism*
  • WT1 Proteins / genetics
  • WT1 Proteins / metabolism*

Substances

  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • WT1 Proteins
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • TERT protein, human
  • Telomerase