Endo Chie, Oda Megumi, Nishiuchi Ritsuo, Seino Yoshiki
Department of Pediatrics, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Pediatr Int. 2003 Jun;45(3):275-80. doi: 10.1046/j.1442-200x.2003.01709.x.
It has recently been shown that t (12;21) (p13;q 22) is the most common molecular genetic abnormality in childhood acute lymphoblastic leukemia (ALL). We have analyzed this translocation in an attempt to evaluate its incidence and to monitor minimal residual disease (MRD) with t (12; 21) rearrangement by detection of TEL-AML1 transcript in patients with childhood ALL.
All cryopreserved bone marrow samples were analyzed using a nested reverse transcription-polymerase chain reaction (RT-PCR) method. TEL-AML1 transcripts were searched for in 34 ALL patients, including six in relapse consecutively diagnosed at our institution between 1991 and 1997.
TEL-AML1 transcripts were found in five (19%) of 27 patients with B precursor ALL. The patients with BCR-ABL, chromosome 11q23 rearrangement and T-ALL patients did not express TEL-AML1 transcripts. Moreover, MRD in five patients with TEL-AML1 transcripts were analyzed in serial samples. Although TEL-AML1 transcripts disappeared soon after the beginning of chemotherapy in three of the five patients, one patient continued to express them for up to 21 months without recurrence and remained in continuous complete remission for seven years after the cessation of chemotherapy. The remaining patient was admitted to our hospital after the second relapse but died following a failure to induce complete remission.
For most patients, the presence of TEL-AML1 transcripts suggests excellent chemosensitivity and a favorable prognosis, but some patients with these transcripts have a different outcome. The present study suggests the possibility that a persistence of MRD is not necessarily related to a relapse of ALL with TEL-AML1 fusion. The prognostic significance of TEL-AML1 transcript remains controversial. Further studies are needed to evaluate the relation between the TEL-AML1 transcript and prognosis.
最近研究表明，t(12;21)(p13;q22)是儿童急性淋巴细胞白血病（ALL）中最常见的分子遗传异常。我们对这种易位进行了分析，旨在评估其发生率，并通过检测儿童ALL患者中TEL-AML1转录本来监测伴有t(12;21)重排的微小残留病（MRD）。
使用巢式逆转录-聚合酶链反应（RT-PCR）方法分析所有冻存的骨髓样本。在34例ALL患者中检测TEL-AML1转录本，其中包括1991年至1997年间在我们机构连续诊断为复发的6例患者。
在27例B前体ALL患者中有5例（19%）检测到TEL-AML1转录本。伴有BCR-ABL、11号染色体q23重排的患者以及T-ALL患者均未表达TEL-AML1转录本。此外，对5例伴有TEL-AML1转录本的患者的系列样本进行了MRD分析。虽然5例患者中有3例在化疗开始后不久TEL-AML1转录本消失，但1例患者持续表达长达21个月且无复发，化疗停止后持续完全缓解7年。其余1例患者在第二次复发后入院，但诱导完全缓解失败后死亡。
对于大多数患者，TEL-AML1转录本的存在提示化疗敏感性良好且预后良好，但部分携带这些转录本的患者预后不同。本研究提示，MRD持续存在不一定与伴有TEL-AML1融合的ALL复发相关。TEL-AML1转录本的预后意义仍存在争议。需要进一步研究来评估TEL-AML1转录本与预后之间的关系。
