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Blood, 1 July 2007, Vol. 110, No. 1, pp. 380-383.
Prepublished online as a Blood First Edition Paper on March 14, 2007; DOI 10.1182/blood-2006-12-065599.
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Submitted December 27, 2006
Accepted March 8, 2007
The polycomb group BMI-1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia
Mohamad Mohty, Agnes S.M. Yong, Richard M. Szydlo, Jane F. Apperley, and Junia V. Melo*
Department of Hematology, Imperial College, Hammersmith Hospital, London, United Kingdom
* Corresponding author; email: j.melo{at}imperial.ac.uk.
Because the polycomb group gene BMI-1 regulates the proliferation of both normal and leukemic stem cells, we examined whether BMI-1 expression was associated with disease progression in chronic myeloid leukemia (CML). Levels of BMI-1 RNA were significantly higher in patients with advanced phase than in patients with chronic phase CML in both CD34+ cells (P=0.006) and total peripheral blood mononuclear cells (P<0.0001). E2F-1, a transcription factor regulating BMI-1, was upregulated in CML as compared to controls (P=0.001). In a cohort of 64 CML patients, the level of BMI-1 at diagnosis correlated with time to transformation to blast crisis, and the combination of low BMI-1 and high proteinase-3 expression was associated in multivariate analysis with an improved overall survival (P=0.001). We conclude that BMI-1 may be a biomarker for the intrinsic heterogeneity of CML, and its measurement at diagnosis can help predict overall survival and thus contribute to better therapeutic decisions.
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