Cayuela J M, Baruchel A, Orange C, Madani A, Auclerc M F, Daniel M T, Schaison G, Sigaux F
Department of Clinical Hematology, Hôpital Saint-Louis, Paris, France.
Blood. 1996 Jul 1;88(1):302-8.
It has recently been shown that the t(12;21)(p13;q22) translocation fuses two genes, TEL on chromosome 12 and AML1 on chromosome 21. We have evaluated the frequency of this newly described translocation in acute lymphoblastic leukemia (ALL), and the feasibility of minimal residual disease (MRD) monitoring by polymerase chain reaction (PCR) amplification of TEL-AML1 transcripts. Thirty-nine adult- and 45 childhood-ALLs consecutively diagnosed in a single center were included in this study. TEL-AML1 fusion transcripts were searched for in the 39 adult- and 45 childhood-ALLs for which material was available. BCR-ABL, E2A-PBX1, and MLL-AF4 transcripts were also studied by PCR in these cases. TEL-AML1 transcripts were found in 8 out of 35 (23%) childhood B-cell precursor ALLs (BCP-ALLs). TEL-AML1 transcripts were detected in only 1 of 31 adult BCP-ALLs (P = .04, Fisher's exact test). Nevertheless, in this adult case, TEL-AML1 transcripts were found at a low level in 2 of 3 different samples. BCR-ABL, E2A-PBX1, and MLL-AF4 transcripts were found in 12, 3, and 1 cases of 31 adult BCP-ALLs, and in 1, 2, and 1 cases of 35 childhood BCP-ALLs, respectively. TEL-AML1 transcripts were never found associated with any other fusion transcripts. Taken together, the four types of chimeric transcripts were detected in 12 of 35 (34%) childhood BCP-ALL cases. No TEL-AML1 transcripts were detected in 11 T-cell ALLs (4 adults and 5 children), nor in 2 B-cell (slg+) ALLs. MRD was evaluated in 21 samples collected in 9 TEL-AML1+ childhood BCP-ALL cases during therapy (median follow-up = 200 days). Of 8 patients evaluated after induction therapy, 4 showed detectable but low levels of MRD. Of 7 patients serially evaluated, only one showed persistence of detectable MRD. This study shows that TEL-AML1 transcripts are frequently detected in pediatric BCP-ALLs and that these transcripts are molecular targets that will simplify the strategy of MRD monitoring in childhood BCP-ALL.
最近研究表明，t(12;21)(p13;q22)易位会使位于12号染色体上的TEL基因和位于21号染色体上的AML1基因融合。我们评估了这种新描述的易位在急性淋巴细胞白血病（ALL）中的发生频率，以及通过聚合酶链反应（PCR）扩增TEL-AML1转录本来监测微小残留病（MRD）的可行性。本研究纳入了在单一中心连续诊断的39例成人ALL和45例儿童ALL。在有样本的39例成人ALL和45例儿童ALL中检测TEL-AML1融合转录本。这些病例还通过PCR研究了BCR-ABL、E2A-PBX1和MLL-AF4转录本。在35例儿童B细胞前体ALL（BCP-ALL）中，有8例（23%）检测到TEL-AML1转录本。在31例成人BCP-ALL中，仅1例检测到TEL-AML1转录本（P = 0.04，Fisher精确检验）。然而，在这例成人病例中，3个不同样本中的2个检测到低水平的TEL-AML1转录本。在31例成人BCP-ALL中，分别有12例、3例和1例检测到BCR-ABL、E2A-PBX1和MLL-AF4转录本；在35例儿童BCP-ALL中，分别有1例、2例和1例检测到这些转录本。从未发现TEL-AML1转录本与任何其他融合转录本相关。综上所述，在35例儿童BCP-ALL病例中，有12例（34%）检测到这四种嵌合转录本。在11例T细胞ALL（4例成人和5例儿童）以及2例B细胞（slg+）ALL中均未检测到TEL-AML1转录本。在9例TEL-AML1阳性儿童BCP-ALL病例治疗期间收集的21份样本中评估了MRD（中位随访时间 = 200天）。在诱导治疗后评估的8例患者中，4例显示可检测到但水平较低的MRD。在7例连续评估的患者中，只有1例显示可检测到的MRD持续存在。本研究表明，TEL-AML1转录本在儿童BCP-ALL中经常被检测到，并且这些转录本是分子靶点，将简化儿童BCP-ALL中MRD监测的策略。
