Carapeti M, Aguiar R C, Goldman J M, Cross N C
Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Blood. 1998 May 1;91(9):3127-33.
Chromosomal abnormalities of band 8p11 are associated with a distinct subtype of acute myeloid leukemia with French-American-British M4/5 morphology and prominent erythrophagocytosis by the blast cells. This subtype is usually associated with the t(8;16)(p11;p13), a translocation that has recently been shown to result in a fusion between the MOZ and CBP genes. We have cloned the inv(8)(p11q13), an abnormality associated with the same leukemia phenotype, and found a novel fusion between MOZ and the nuclear receptor transcriptional coactivator TIF2/GRIP-1/NCoA-2. This gene has not previously been implicated in the pathogenesis of leukemia or other malignancies. MOZ-TIF2 retains the histone acetyltransferase homology domains of both proteins and also the CBP binding domain of TIF2. We speculate that the apparently identical leukemia cell phenotype observed in cases with the t(8;16) and the inv(8) arises by recruitment of CBP by MOZ-TIF2, resulting in modulation of the transcriptional activity of target genes by a mechanism involving abnormal histone acetylation.
8p11染色体异常与一种具有独特亚型的急性髓系白血病相关，该亚型具有法美英协作组（French-American-British）M4/5形态，且原始细胞有明显的红细胞吞噬现象。这种亚型通常与t(8;16)(p11;p13)相关，最近的研究表明，这种易位会导致MOZ和CBP基因融合。我们克隆了inv(8)(p11q13)，这是一种与相同白血病表型相关的异常，并且发现了MOZ与核受体转录共激活因子TIF2/GRIP-1/NCoA-2之间的新型融合。该基因以前未被认为与白血病或其他恶性肿瘤的发病机制有关。MOZ-TIF2保留了两种蛋白质的组蛋白乙酰转移酶同源结构域以及TIF2的CBP结合结构域。我们推测，在t(8;16)和inv(8)病例中观察到的明显相同的白血病细胞表型，是由MOZ-TIF2招募CBP导致的，通过一种涉及异常组蛋白乙酰化的机制，从而调节靶基因的转录活性。
