Detection of Fusion Transcripts Generated by the Inversion 16 Chromosome in Acute Myelogenous Leukemia

Detection of Fusion Transcripts Generated by the Inversion 16 Chromosome in Acute Myelogenous Leukemia
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急性髓性白血病中 16 号染色体倒位产生的融合转录本的检测

DOI:
10.1182/blood.v83.7.1750.bloodjournal8371750
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发表时间:
1994
期刊:
影响因子:
20.3
通讯作者:
M. Siciliano
M. Siciliano
中科院分区:
医学1区
文献类型:
--
作者:
D. Claxton;P. Liu;H. Hsu;P. Marlton;J. Hester;F. Collins;A. Deisseroth;J. Rowley;M. Siciliano

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16 号染色体的中心周倒位 [inv(16)(p13q22)] 和相关的 t(16;16)(p13;q22) 在急性髓性白血病 (AML) 亚型中可见,其表型和预后与其他病例不同。我们最近表明,inv(16) 导致 CBFB/PEBP2B(16q22 编码的基因)与 MYH11(16p13 编码的平滑肌肌球蛋白重链基因)融合。由与下游 MYH11 编码序列融合的上游 CBFB 组成的嵌合转录物是由这种融合产生的。在这项研究中,我们使用逆转录酶聚合酶链式反应 (RT-PCR) 检测了 37 个此类病例,以检测杂合 CBFB/MYH11 转录物的表达。在 37 例具有典型 inv(16) 或 t(16;16) 的白血病中,除 1 例外,其余所有病例均检测到嵌合 cDNA。在具有 inv(16)(p13q24)(即变异 q 臂断点)的病例或 10 例没有这些染色体变化的 AML 病例中没有观察到此类嵌合产物。发现了四种不同的嵌合转录物,代表 MYH11 内剪接至 CBFB 位置 495 的不同融合点。描述了用于有效扩增这些不同 cDNA 形式的引物组。 cDNA 扩增表明,CBFB 编码序列中除 17 个密码子外的所有密码子均包含在异常转录本中。 RT-PCR 被证明具有高度敏感性,并且对于形态学缓解期间的白血病细胞的检测可能有用。
Pericentric inversion of chromosome 16 [inv(16)(p13q22)] and the related t(16;16)(p13;q22) are seen in a subset of acute myelogenous leukemia (AML) phenotypically and prognostically differing from other cases. We have recently shown that inv(16) results in fusion of CBFB/PEBP2B, a gene encoded at 16q22 to MYH11, a smooth muscle myosin heavy chain gene encoded at 16p13. Chimeric transcripts consisting of upstream CBFB fused to downstream MYH11 coding sequences result from this fusion. In this study we have examined a series of 37 of these cases using reverse transcriptase-polymerase chain reaction (RT-PCR) to detect expression of a hybrid CBFB/MYH11 transcript. Chimeric cDNAs were detected in all but 1 of 37 leukemias with typical inv(16) or t(16;16). Such chimeric products were not seen in a case with inv(16)(p13q24) (ie, a variant q arm breakpoint) or any of 10 cases of AML without these chromosomal changes. Four different chimeric transcripts were found, representing differing fusion points within MYH11 spliced to position 495 of CBFB. Primer sets are described for efficient amplification of these different cDNA forms. Amplification of cDNA showed that all but 17 codons of the CBFB coding sequence are included in the abnormal transcripts. RT-PCR was shown to be highly sensitive and potentially useful for detection of leukemic cells during morphologic remission.
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