Loh M L, Silverman L B, Young M L, Neuberg D, Golub T R, Sallan S E, Gilliland D G
Division of Hematology-Oncology, Brigham and Women's Hospital, Department of Pediatric Oncology the Dana-Farber Cancer Institute, Boston, MA, USA.
Blood. 1998 Dec 15;92(12):4792-7.
The TEL/AML1 fusion associated with t(12;21)(p13;q22) is the most common gene rearrangement in childhood leukemia, occurring in approximately 25% of pediatric acute lymphoblastic leukemia (ALL), and is associated with a favorable prognosis. For example, a cohort of pediatric patients with ALL retrospectively analyzed for the TEL/AML1 fusion treated on Dana-Farber Cancer Institute (DFCI) ALL Consortium protocols between 1980 to 1991 demonstrated a 100% relapse-free survival in TEL/AML1-positive patients with a median of 8.3 years of follow-up. However, two recent studies analyzing pediatric patients with relapsed ALL have reported the same incidence of the TEL/AML1 rearrangement as in patients with newly diagnosed ALL, suggesting that TEL/AML1 positivity is not a favorable prognostic indicator. To clarify this apparent discrepancy, 48 pediatric patients treated on Dana-Farber Cancer Institute (DFCI) protocols with ALL at first or second relapse were tested for TEL/AML1 using reverse transcriptase-polymerase chain reaction (RT-PCR). The TEL/AML1 fusion was identified in only 1 of 32 analyzable relapsed ALL patients, in concordance with our previous reports of improved disease-free survival in TEL/AML1-positive patients. The low frequency of TEL/AML1-positive patients at relapse is significantly different than that reported in other studies. Although there are several potential explanations for the observed differences in TEL/AML1-positive patients at relapse, it is plausible that relapse-free survival in TEL/AML1-positive patients may be changed with different therapeutic approaches. Taken together, these results support the need for prospective analysis of prognosis in TEL/AML1-positive patients.
与t(12;21)(p13;q22)相关的TEL/AML1融合是儿童白血病中最常见的基因重排，约见于25%的小儿急性淋巴细胞白血病（ALL），且与良好的预后相关。例如，一组在1980年至1991年间按照达纳-法伯癌症研究所（DFCI）ALL协作组方案接受治疗的小儿ALL患者，经回顾性分析TEL/AML1融合情况，结果显示TEL/AML1阳性患者的无复发生存率为100%，中位随访时间为8.3年。然而，最近两项分析复发ALL小儿患者的研究报告称，TEL/AML1重排的发生率与新诊断ALL患者相同，这表明TEL/AML1阳性并非良好的预后指标。为了阐明这一明显的差异，我们使用逆转录聚合酶链反应（RT-PCR）对48例按照DFCI方案接受治疗的首次或第二次复发的小儿ALL患者进行了TEL/AML1检测。在32例可分析的复发ALL患者中，仅1例检测到TEL/AML1融合，这与我们之前关于TEL/AML1阳性患者无病生存率提高的报告一致。复发时TEL/AML1阳性患者的低频率与其他研究报告的情况显著不同。尽管对于复发时TEL/AML1阳性患者观察到的差异有几种可能的解释，但TEL/AML1阳性患者的无复发生存率可能会因不同的治疗方法而改变，这似乎是合理的。综上所述，这些结果支持对TEL/AML1阳性患者的预后进行前瞻性分析。
