title: The polycomb group BMI1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia.
abstract: Because the polycomb group gene BMI1 regulates the proliferation of both normal and leukemic stem cells, we examined whether BMI1 expression was associated with disease progression in chronic myeloid leukemia (CML). Levels of BMI1 RNA were significantly higher in patients with advanced-phase than in patients with chronic-phase CML in both CD34(+) cells (P = .006) and total peripheral-blood mononuclear cells (P < .001). E2F1, a transcription factor regulating BMI1, was up-regulated in CML compared with controls (P = .001). In a cohort of 64 CML patients, the level of BMI1 at diagnosis correlated with time to transformation to blast crisis, and the combination of low BMI1 and high proteinase-3 expression was associated in multivariate analysis with an improved overall survival (P = .001). We conclude that BMI1 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.
authors.affiliation: Department of Hematology, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.forename: Agnes S M
authors.initials: AS
authors.lastname: Yong
authors.forename: Richard M
authors.initials: RM
authors.lastname: Szydlo
authors.forename: Jane F
authors.initials: JF
authors.lastname: Apperley
authors.forename: Junia V
authors.initials: JV
authors.lastname: Melo
mesh_terms: D018952:Antigens, CD34; D014408:Biomarkers, Tumor / Q000032:analysis; D001752:Blast Crisis; D016022:Case-Control Studies; D018450:Disease Progression; D050687:E2F1 Transcription Factor / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000209:etiology*; D007962:Leukocytes / Q000737:chemistry; D053146:Myeloblastin / Q000235:genetics; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics*; D063150:Polycomb Repressive Complex 1; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D012334:RNA, Neoplasm / Q000032:analysis; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics*; D012720:Severity of Illness Index; D016019:Survival Analysis; D015854:Up-Regulation / Q000235:genetics
chemical_list: D018952:Antigens, CD34; C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1; D053146:Myeloblastin