Wlodarska I, Mecucci C, Marynen P, Guo C, Franckx D, La Starza R, Aventin A, Bosly A, Martelli M F, Cassiman J J
Center for Human Genetics, University of Leuven, Belgium.
Blood. 1995 May 15;85(10):2848-52.
A t(5;12)(q33;p13) translocation is a recurrent chromosome abnormality in a subgroup of myeloid malignancies with features of both myeloproliferative disorders and myelodysplastic syndromes (MDSs). The molecular consequence of a t(5;12) is a fusion between the platelet-derived growth factor receptor-B gene on chromosome 5 and a novel ETS-like gene, TEL, on chromosome 12. We report on three patients with a t(5;12)(q33;p13) diagnosed as chronic myelomonocytic leukemia, and one case of a t(10;12)(q24;p13) in a progressive MDS, with eosinophilia and monocytosis. Involvement of the TEL gene in these chromosome translocations was investigated by fluorescence in situ hybridization (FISH) with cosmid probes containing selectively the 5' end or 3' end of TEL. Hybridization of these cosmids to the der(5)/der(10) or a der(12), respectively, demonstrated a rearrangement of TEL in both translocations, showing that the t(10;12) is a variant translocation of the t(5;12). Cloning of the fusion cDNA of one case of t(5;12) showed that the breakpoint occurred at the RNA level at exactly the same position as reported by Golub et al (Cell 77:307, 1994). In addition, the TEL gene on chromosome 12 could be localized between two probes previously mapped to 12p13, namely PRB1 and D12S178, leading to a better definition of the position of TEL in this chromosome region. Moreover, in the case involving chromosome 10, the breakpoint occurred between cKTN206 and cKTN312/LYT-10 at 10q24. Clinicohematological data in these studies as well as the restriction mapping of chromosomal breakpoints strongly suggest that (1) common features in MDSs involving the TEL gene are monocytosis and eosinophilia, (2) chromosomes other than no. 5 may be involved and at least a t(10;12)(q24;p13) variant chromosome translocation does exist in these MDSs, and (3) both standard and variant 12p/TEL translocations may be identified by FISH with appropriate probes.
t(5;12)(q33;p13)易位是髓系恶性肿瘤一个亚组中常见的染色体异常，该亚组具有骨髓增殖性疾病和骨髓增生异常综合征（MDS）的特征。t(5;12)的分子后果是5号染色体上的血小板衍生生长因子受体-B基因与12号染色体上一个新的ETS样基因TEL融合。我们报告了3例诊断为慢性粒单核细胞白血病的t(5;12)(q33;p13)患者，以及1例进展性MDS伴嗜酸性粒细胞增多和单核细胞增多的t(10;12)(q24;p13)病例。通过用含有TEL 5'端或3'端的黏粒探针进行荧光原位杂交（FISH），研究了TEL基因在这些染色体易位中的情况。这些黏粒分别与der(5)/der(10)或der(12)杂交，证实了两种易位中TEL均发生重排，表明t(10;12)是t(5;12)的变异易位。1例t(5;12)融合cDNA的克隆显示，断点发生在RNA水平，位置与Golub等人（《细胞》77:307, 1994）报道的完全相同。此外，12号染色体上的TEL基因可定位在先前定位于12p13的两个探针PRB1和D12S178之间，从而更好地确定了TEL在该染色体区域的位置。此外，在涉及10号染色体的病例中，断点发生在10q24的cKTN206和cKTN312/LYT-10之间。这些研究中的临床血液学数据以及染色体断点的限制性图谱有力地表明：（1）涉及TEL基因的MDS的共同特征是单核细胞增多和嗜酸性粒细胞增多；（2）除5号染色体外的其他染色体可能受累，且这些MDS中至少存在一种t(10;12)(q24;p13)变异染色体易位；（3）使用合适的探针通过FISH可识别标准和变异的12p/TEL易位。
