Rogaia D, Grignani F, Carbone R, Riganelli D, LoCoco F, Nakamura T, Croce C M, Di Fiore P P, Pelicci P G
European Institute of Oncology, Department of Experimental Oncology, Milan, Italy.
Cancer Res. 1997 Mar 1;57(5):799-802.
Translocations involving the HRX/ALL1 locus at chromosomal region 11q23 are among the most frequent cytogenetic abnormalities in acute leukemias. 11q23 translocations involve different chromosome partners and lead to the formation of HRX/ALL1 fusion proteins. The HRX/ALL1 protein is a putative transcription factor that has been implicated in developmental regulation in mammals. We report here the cellular localization of the HRX/ALL1 protein as well as that of the HRX/ALL1-eps15 fusion protein, the result of the t(1;11) (p32-q23) translocation of acute myeloid leukemias. The HRX/ALL1 protein was localized to both the cytoplasm and the nucleus. The nuclear pattern was characterized by diffuse staining, perinuclear accumulation, and localization within nuclear bodies of variable size, morphology, and number. The HRX/ALL1-eps15 localized exclusively to the nucleus within bodies that were smaller and more numerous than the HRX/ALL1 nuclear bodies. HRX/ALL1 fusion with an unknown partner in leukemia blasts with 11q23 abnormalities had similar morphological features. Thus, the fusion with eps15 alters the cellular compartmentalization of HRX/ALL1, providing a putative mechanism for activation of HRX/ALL1 by 11q23 abnormalities.
涉及染色体区域11q23上HRX/ALL1基因座的易位是急性白血病中最常见的细胞遗传学异常之一。11q23易位涉及不同的染色体伙伴，并导致HRX/ALL1融合蛋白的形成。HRX/ALL1蛋白是一种推定的转录因子，与哺乳动物的发育调控有关。我们在此报告HRX/ALL1蛋白以及HRX/ALL1-eps15融合蛋白（急性髓性白血病t(1;11)(p32-q23)易位的结果）的细胞定位。HRX/ALL1蛋白定位于细胞质和细胞核。核模式的特征是弥漫性染色、核周聚集以及定位于大小、形态和数量各异的核小体内。HRX/ALL1-eps15仅定位于细胞核内的小体中，这些小体比HRX/ALL1核小体更小且数量更多。在具有11q23异常的白血病母细胞中，HRX/ALL1与未知伙伴的融合具有相似的形态特征。因此，与eps15的融合改变了HRX/ALL1的细胞区室化，为11q23异常激活HRX/ALL1提供了一种推定机制。
