Tandem duplication of the FLT3 gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children
Tandem duplication of the FLT3 gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children
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DOI：
10.1111/j.1365-2141.1999.01284.x
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发表时间：
1999-04-01
影响因子：
6.5
通讯作者：
Hayashi, Y
中科院分区：
文献类型：
--
作者：
Xu, F;Taki, T;Hayashi, Y
我们通过逆转录聚合酶链式反应 (RT-PCR) 和基因组 PCR 以及测序，检查了血液恶性肿瘤中 Fms 样酪氨酸激酶 3 (FLT3) 基因的 mRNA 表达和内部串联重复。通过RT-PCR，在45/74（61%）的白血病细胞系中检测到FLT3的表达，且未分化型（B前体急性淋巴细胞白血病；ALL）中FLT3的表达频率显着高于分化型细胞系（B-ALL）（P=0.0076）。采用基因组PCR方法对194份新鲜样本进行了检查，其中包括87例急性髓系白血病、60例ALL、32例骨髓增生异常综合征（MDS）和15例幼年慢性粒细胞白血病（JCML）。在 12 例 (13.8%) AML 和 2 例 (3.3%) ALL 中发现串联重复。对 14 个重复样本的序列分析显示，8 个显示简单串联重复，6 个显示插入串联重复。这些串联重复大多数发生在外显子11内，并且从外显子II到内含子II和外显子12发生两次重复。在MDS或JCML中未检测到FLT3基因的串联重复。儿童 AMT 中 FLT3 基因串联重复的频率低于迄今为止报道的成人 AML 中的频率。 12 名具有重复的 AML 患者在诊断后 47 个月内全部死亡，而两名具有重复的 ALL 患者分别存活了 44 个月和 72 个月。这两名 ALL 患者同时表达淋巴和骨髓抗原，被认为患有双表型白血病。这些结果表明，除了AML之外，串联重复还涉及ALL，但不涉及儿童MDS或JCML，并且存在串联重复的儿童AML患者预后不良。
We examined mRNA expression and internal tandem duplication of the Fms-like tyrosine kinase 3 (FLT3) gene in haematological malignancies by reverse transcriptase-polymerase chain reaction (RT-PCR) and genomic PCR followed by sequencing. By RT-PCR, expression of FLT3 was detected in 45/74 (61%) leukaemia cell lines and the frequency of expression of FLT3 was significantly higher in undifferentiated type (B-precursor acute lymphoblastic leukaemia; ALL) than in differentiated type cell lines (B-ALL) (P=0.0076). Using the genomic PCR method, 194 fresh samples including 87 acute myeloid leukaemias, 60 ALLs, 32 myelodysplastic syndromes (MDSs) and 15 juvenile chronic myelogenous leukaemias (JCMLs) were examined. Tandem duplication was found in 12 (13.8%) AMLs and two (3.3%) ALLs. Sequence analyses of the 14 samples with the duplication revealed that eight showed a simple tandem duplication and six a tandem duplication with insertion. Most of these tandem duplications occurred within exon 11, and two duplications occurred from exon II to intron II and exon 12. No tandem duplications of FLT3 gene were detected in MDS or JCML. The frequency of tandem duplication of FLT3 gene in childhood AMT, was lower than that in adult AML so far reported. All of the 12 AML patients with the duplication died within 47 months after diagnosis, whereas two ALL patients with the duplication have survived 44 and 72 months, respectively. These two ALL patients expressed both lymphoid and myeloid antigens and were considered to have biphenotypic leukaemia. These results suggest that tandem duplication is involved in ALL in addition to AML, but not in childhood MDS or JCML, and that childhood AML patients with the tandem duplication have a poor prognosis.