Mohty Mohamad, Yong Agnes S M, Szydlo Richard M, Apperley Jane F, Melo Junia V
Department of Hematology, Imperial College London, Hammersmith Hospital, London, United Kingdom.
Blood. 2007 Jul 1;110(1):380-3. doi: 10.1182/blood-2006-12-065599. Epub 2007 Mar 14.
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.
由于多梳蛋白家族基因BMI1可调控正常干细胞和白血病干细胞的增殖，我们研究了BMI1表达是否与慢性髓性白血病（CML）的疾病进展相关。在CD34(+)细胞（P = .006）和外周血单个核细胞（P < .001）中，晚期慢性髓性白血病患者的BMI1 RNA水平显著高于慢性期患者。与对照组相比，CML中调控BMI1的转录因子E2F1上调（P = .001）。在64例CML患者队列中，诊断时的BMI1水平与急变期转化时间相关，多因素分析显示，低BMI1和高蛋白酶-3表达的联合与总体生存率提高相关（P = .001）。我们得出结论，BMI1可能是CML内在异质性的生物标志物，诊断时对其进行检测有助于预测总体生存率，从而有助于做出更好的治疗决策。
Zotero 插件