Sawa Masashi, Yamamoto Kazuhito, Yokozawa Toshiya, Kiyoi Hitoshi, Hishida Asahi, Kajiguchi Tomohiro, Seto Masao, Kohno Akio, Kitamura Kunio, Itoh Yoshie, Asou Norio, Hamajima Nobuyuki, Emi Nobuhiko, Naoe Tomoki
Department of Molecular Medicine and Hematology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Int J Hematol. 2005 Jul;82(1):42-7. doi: 10.1532/IJH97.05013.
Recent studies have suggested that one of the polycomb group genes, BMI-1, has an important role in the maintenance of normal and leukemic stem cells by repressing the INK4a/ARF locus. Here, we quantitatively examined BMI-1 expression level in samples from patients with acute myeloid leukemia (AML) and other hematologic malignancies. Moderate to high BMI-1 expression was detected in AML patients, and the BMI-1 expression levels in AML samples were significantly higher than in normal bone marrow controls (P = .0011). Specimens of French-American-British classification subtype M0 showed higher relative expression of the BMI-1 transcript (median, 390.2 3 10(-3)) than the other subtypes (median, 139.0 3 10(-3)) (P < .0001). Leukemia other than AML showed low to moderate expression. INK4a-ARF transcript expression tended to be inverse proportion to that of BMI-1. In an M0 patient with a high BMI-1 transcript level, the INK4a-ARF transcript level fell promptly and maintained a low value after the patient achieved complete remission. These results indicated that a subgroup of M0 patients has a high expression level of polycomb group gene BMI-1, which may contribute to leukemogenesis.
最近的研究表明,多梳蛋白家族基因之一BMI-1,通过抑制INK4a/ARF基因座,在维持正常干细胞和白血病干细胞中发挥重要作用。在此,我们定量检测了急性髓系白血病(AML)患者及其他血液系统恶性肿瘤患者样本中BMI-1的表达水平。在AML患者中检测到中度至高BMI-1表达,且AML样本中的BMI-1表达水平显著高于正常骨髓对照(P = 0.0011)。法国-美国-英国(FAB)分类亚型M0的标本显示BMI-1转录本的相对表达较高(中位数,390.2×10⁻³),高于其他亚型(中位数,139.0×10⁻³)(P < 0.0001)。非AML的白血病显示低至中度表达。INK4a-ARF转录本表达倾向于与BMI-1呈反比。在一名BMI-1转录本水平高的M0患者中,INK4a-ARF转录本水平在患者达到完全缓解后迅速下降并维持在低水平。这些结果表明,M0患者亚组具有多梳蛋白家族基因BMI-1的高表达水平,这可能有助于白血病的发生。