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Sensitivity to imatinib therapy may be predicted by testing Wilms tumor gene expression and colony growth after a short in vitro incubation
Article first published online: 23 JUL 2004
Copyright © 2004 American Cancer Society
Volume 101, Issue 5, pages 979–988, 1 September 2004
How to Cite
Cilloni, D., Messa, F., Gottardi, E., Fava, M., Arruga, F., Defilippi, I., Carturan, S., Messa, E., Morotti, A., Giugliano, E., Rege-Cambrin, G., Alberti, D., Baccarani, M. and Saglio, G. (2004), Sensitivity to imatinib therapy may be predicted by testing Wilms tumor gene expression and colony growth after a short in vitro incubation. Cancer, 101: 979–988. doi: 10.1002/cncr.20457
- Issue published online: 18 AUG 2004
- Article first published online: 23 JUL 2004
- Manuscript Revised: 24 MAY 2004
- Manuscript Accepted: 24 MAY 2004
- Manuscript Received: 21 JAN 2004
- Consiglio Nazionale delle Ricerche (Progetto Finalizzato Oncologia)
- Ministero dell'Istruzione, dell'Università, e della Ricerca (COFIN 2003)
- Associazione Italiana contro le Leucemie
- Associazione Italiana per la Ricerca sul Cancro
- Regione Piemonte
- chronic myelogenous leukemia;
- bone marrow samples
The objective of the current study was to verify the ability to predict response to imatinib therapy using in vitro assays to evaluate the inhibition of Wilms tumor gene (WT1) expression and colony growth after samples obtained from patients with chronic myelogenous leukemia (CML) before the start of treatment were subjected to short-term incubation with imatinib.
WT1 transcript levels and colony growth in bone marrow (BM) samples from 23 patients with CML that was later identified as being responsive to imatinib and from 13 patients with CML that was later identified as not being responsive to imatinib were evaluated after incubation of these samples with imatinib at a concentration of 1 μM for 18 hours. In addition, real-time quantitative polymerase chain reaction (RQ-PCR) analysis of WT1 expression was performed during follow-up, and the results were analyzed for associations with cytogenetic response and with BCR/ABL transcript levels as determined using RQ-PCR analysis.
Before treatment, it was found that WT1 expression was elevated in BM samples obtained from all patients with CML. WT1 expression and colony growth were reduced significantly after an 18-hour incubation with imatinib in samples obtained from patients who were later identified as responders to treatment, but not in samples obtained from patients who did not experience responses to treatment. Inhibition of WT1 expression in vitro was associated with inhibition of imatinib-induced BCR-ABL tyrosine kinase activity, a finding that also has been made in studies involving certain Philadelphia chromosome (Ph)-positive and Ph-negative cell lines.
Inhibition of WT1 transcript levels after a short period of in vitro exposure of pretherapy BM samples to imatinib was correlated with inhibition of colony growth and may represent the basis for an easy test that is capable of predicting the sensitivity of CML to treatment with imatinib for individual patients. Cancer 2004. © 2004 American Cancer Society.