McLean T W, Ringold S, Neuberg D, Stegmaier K, Tantravahi R, Ritz J, Koeffler H P, Takeuchi S, Janssen J W, Seriu T, Bartram C R, Sallan S E, Gilliland D G, Golub T R
Division of Hematology/Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Blood. 1996 Dec 1;88(11):4252-8.
Polymerase chain reaction-based screening of childhood acute lymphoblastic leukemia (ALL) samples showed that a TEL/AML1 fusion transcript was detected in 27% of all cases, representing the most common known gene rearrangement in childhood cancer. The TEL/AML1 fusion results from a t(12;21)(p13;q22) chromosomal translocation, but was undetectable at the routine cytogenetic level. TEL/AML1-positive patients had exclusively B-lineage ALL, and most patients were between the ages of 2 and 9 years at diagnosis. Only 3/89 (3.4%) adult ALL patients were TEL/AML1-positive. Most importantly, TEL/AML1-positive children had a significantly lower rate of relapse compared with TEL/AML1-negative patients (0/22 v 16/54, P = .004). Co-immunoprecipitation experiments demonstrated that TEL/AML-1 formed homodimers in vitro, and heterodimerized with the normal TEL protein when the two proteins were expressed together. The elucidation of the precise mechanism of transformation by TEL/AML1 and the role of TEL/AML1 testing in the treatment of childhood ALL will require additional studies.
基于聚合酶链反应对儿童急性淋巴细胞白血病（ALL）样本进行的筛查显示，在所有病例中有27%检测到TEL/AML1融合转录本，这是儿童癌症中最常见的已知基因重排。TEL/AML1融合是由t(12;21)(p13;q22)染色体易位导致的，但在常规细胞遗传学水平上无法检测到。TEL/AML1阳性患者均为B系ALL，大多数患者在诊断时年龄在2至9岁之间。89例成人ALL患者中只有3例（3.4%）为TEL/AML1阳性。最重要的是，与TEL/AML1阴性患者相比，TEL/AML1阳性儿童的复发率显著更低（0/22对16/54，P = 0.004）。免疫共沉淀实验表明，TEL/AML-1在体外形成同源二聚体，当两种蛋白共同表达时，它与正常TEL蛋白形成异源二聚体。要阐明TEL/AML1转化的确切机制以及TEL/AML1检测在儿童ALL治疗中的作用，还需要进一步研究。
