Silliman C C, McGavran L, Wei Q, Miller L A, Li S, Hunger S P
Department of Pediatrics, University of Colorado School of Medicine, The Children's Hospital, Denver, USA.
Leukemia. 1998 Sep;12(9):1404-10. doi: 10.1038/sj.leu.2401109.
The t(10;11)(p13;q14-21) is a non-random translocation that occurs primarily in T cell acute lymphoblastic leukemias (T-ALL), but has also been observed in leukemias and lymphomas of diverse lineages. In U937, a cell line established from a diffuse histiocytic lymphoma, a t(10;11)(p13;q14-21) fuses AF10 to CALM. AF10 is also fused to MLL by a translocation that appears quite similar at the cytogenetic level, the t(10;11)(p12;q23). Fluorescence in situ hybridization studies have demonstrated that AF10 and CALM are also involved in other hematological malignancies containing t(10;11)(p13;q21), but no data are available concerning the molecular details of AF10-CALM fusion in primary leukemias. Using RT-PCR, we amplified multiple different isoforms of AF10-CALM and CALM-AF10 fusion cDNAs from a primary T cell ALL containing a t(10;11)(p13-14;q14-21). These cDNAs arose via alternative splicing of exons from both AF10 and CALM, which we demonstrated can also occur in the native genes. We identified at least two novel AF10 exons that can be included in wild-type and fusion cDNAs. The majority of the AF10 and AF10-CALM cDNA isoforms that we identified are predicted to encode for truncated AF10 polypeptides, raising the possibility that these might have important cellular functions in normal and malignant cells, perhaps by acting as dominant negative inhibitors of full-length AF10 or related proteins.
t(10;11)(p13;q14 - 21)是一种非随机易位，主要发生在T细胞急性淋巴细胞白血病（T - ALL）中，但在不同谱系的白血病和淋巴瘤中也有观察到。在U937（一种从弥漫性组织细胞淋巴瘤建立的细胞系）中，t(10;11)(p13;q14 - 21)使AF10与CALM融合。在细胞遗传学水平上，AF10也通过一种看似非常相似的易位t(10;11)(p12;q23)与MLL融合。荧光原位杂交研究表明，AF10和CALM也参与了其他含有t(10;11)(p13;q21)的血液系统恶性肿瘤，但关于原发性白血病中AF10 - CALM融合的分子细节尚无数据。我们使用逆转录聚合酶链反应（RT - PCR），从一例含有t(10;11)(p13 - 14;q14 - 21)的原发性T细胞ALL中扩增出多种不同的AF10 - CALM和CALM - AF10融合cDNA异构体。这些cDNA是通过AF10和CALM外显子的选择性剪接产生的，我们证明这在天然基因中也会发生。我们鉴定出至少两个可包含在野生型和融合cDNA中的新型AF10外显子。我们鉴定出的大多数AF10和AF10 - CALM cDNA异构体预计编码截短的AF10多肽，这增加了这些多肽可能在正常和恶性细胞中具有重要细胞功能的可能性，也许是通过作为全长AF10或相关蛋白的显性负性抑制剂发挥作用。
