The t(4;22)(q12;q11) in atypical chronic myeloid leukaemia fuses BCR to PDGFRA
The t(4;22)(q12;q11) in atypical chronic myeloid leukaemia fuses BCR to PDGFRA
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DOI：
10.1093/hmg/11.12.1391
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发表时间：
2002-06-01
影响因子：
3.5
通讯作者：
Cross, NCP
中科院分区：
文献类型：
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作者：
Baxter, EJ;Hochhaus, A;Cross, NCP
慢性粒细胞白血病（CML）的特征是存在BCR-ABL融合基因，通常与t（9;22）（q34;q11）易位相关。我们在这里报告了两名CML样骨髓增生性疾病（MPD）患者中发现和克隆了一种罕见的变异易位t（4;22）（q12;q11）。RT-PCR检测结果均为BCR-ABL阴性，FISH检测结果提示BCR基因重排。由于MPD中的其他易位经常涉及酪氨酸激酶，我们设计了一种多重PCR来搜索BCR和4 q12处的三个潜在伴侣基因：KIT，KDR和PDGFRA之间的mRNA融合。在两名患者中发现了一种不寻常的框内BCR-PDGFRA融合mRNA，BCR外显子7或外显子12与短BCR内含子衍生序列融合，后者又与PDGFRA外显子12的一部分融合。基因组断裂点连接的测序显示，22号染色体断裂点位于BCR内含子中，而4号染色体断裂点位于PDGFRA外显子12内。这是第一个涉及PDGFRA的融合基因的报道。我们的研究结果表明，明显简单的t（9;22）细胞遗传学变异并不总是掩盖一个神秘的BCR-ABL融合，即使发现与临床和血液学的CML适应症。
Chronic myeloid leukaemia (CML) is characterized by the presence of the BCR-ABL fusion gene, usually in association with the t(9;22)(q34;q11) translocation. We report here the identification and cloning of a rare variant translocation, t(4;22)(q12;q11), in two patients with a CML-like myeloproliferative disease (MPD). RT-PCR indicated that both patients were negative for BCR-ABL, but FISH analysis suggested that the BCR gene was rearranged. Since other translocations in MPDs frequently involve tyrosine kinases, we designed a multiplex PCR to search for mRNA fusions between BCR and three potential partner genes at 4q12: KIT, KDR and PDGFRA. An unusual inframe BCR-PDGFRA fusion mRNA was identified in both patients, with either BCR exon 7 or exon 12 fused to short BCR intron-derived sequences, which were in turn fused to part of PDGFRA exon 12. Sequencing of the genomic breakpoint junctions showed that the chromosome 22 breakpoints fell in BCR introns whereas the chromosome 4 breakpoints were within PDGFRA exon 12. This is the first report of a fusion gene that involves PDGFRA. Our findings indicate that apparently simple cytogenetic variants of t(9;22) do not always mask a cryptic BCR-ABL fusion, even when found in association with clinical and haematological indications of CML.