Kim D H, Moldwin R L, Vignon C, Bohlander S K, Suto Y, Giordano L, Gupta R, Fears S, Nucifora G, Rowley J D
Department of Pediatrics, University of Chicago IL, USA.
Blood. 1996 Aug 1;88(3):785-94.
The t(12;21) (p 13; q22) results in the fusion of the TEL gene located on chromosome 12 with the AML1 gene located on the derivative chromosome 21. Because this translocation is difficult to detect using standard cytogenetic techniques, 27 previously karyotyped B-lineage acute lymphoblastic leukemia (ALL) cell lines were evaluated for the presence of the TEL-AML1 fusion using the reverse transcriptase-polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), and cDNA sequencing. Six cell lines expressed the TEL-AML1 chimeric transcript by RT-PCR and the t(12;21) was confirmed by FISH analysis with probes for TEL, AML1, and chromosome 12. While only one of the 6 cell lines with the t(12;21) lost the der(12)t(12;21)-encoded AML1-TEL fusion transcript, 4 cell lines lacked expression of the nontranslocated allele of TEL and 5 cell lines lacked expression of CDKN2. Moreover, in 2 patients (1 with the TEL-AML1 transcript and 1 without), TEL expression was lost with disease progression; le, TEL was expressed in the initial cell lines (established at diagnosis or first relapse) whereas TEL was not expressed in the cell lines established from these patients in late-stage disease. These data show the coexistence of multiple genetic defects in childhood B-lineage ALL Cell lines with t(12;21) will facilitate the study of TEL-AML1 and AML1-TEL fusion proteins as well as TEL and CDKN2 gene inactivation in leukemia transformation and progression.
t(12;21) (p13;q22)导致位于12号染色体上的TEL基因与位于衍生21号染色体上的AML1基因融合。由于使用标准细胞遗传学技术难以检测到这种易位，因此使用逆转录聚合酶链反应（RT-PCR）、荧光原位杂交（FISH）和cDNA测序对27个先前进行过核型分析的B系急性淋巴细胞白血病（ALL）细胞系进行了TEL-AML1融合的检测。6个细胞系通过RT-PCR表达了TEL-AML1嵌合转录本，并且通过使用针对TEL、AML1和12号染色体的探针进行FISH分析证实了t(12;21)。虽然6个具有t(12;21)的细胞系中只有1个丢失了der(12)t(12;21)编码的AML1-TEL融合转录本，但有4个细胞系缺乏TEL非易位等位基因的表达，5个细胞系缺乏CDKN2的表达。此外，在2例患者中（1例有TEL-AML1转录本，1例没有），TEL表达随着疾病进展而丢失；也就是说，TEL在初始细胞系（诊断时或首次复发时建立）中表达，而在这些患者晚期疾病建立的细胞系中不表达。这些数据表明，儿童B系ALL细胞系中存在多种遗传缺陷，t(12;21)将有助于研究TEL-AML1和AML1-TEL融合蛋白以及TEL和CDKN2基因失活在白血病转化和进展中的作用。
