Spectral karyotyping in patients with acute myeloid leukemia and a complex karyotype shows hidden aberrations, including recurrent overrepresentation of 21q, 11q, and 22q
Spectral karyotyping in patients with acute myeloid leukemia and a complex karyotype shows hidden aberrations, including recurrent overrepresentation of 21q, 11q, and 22q
复制标题
DOI：
10.1002/gcc.10027
复制
发表时间：
2002-06-01
影响因子：
3.7
通讯作者：
Bloomfield, CD
中科院分区：
文献类型：
--
作者：
Mrózek, K;Heinonen, K;Bloomfield, CD
我们使用光谱核型分析（SKY）研究了29例成人急性髓性白血病和一个复杂的核型包含一个到九个异常，不能完全识别的G显带。SKY在所有情况下都显示了不平衡易位中的环和未识别物质的起源，并且在大多数情况下显示了标记的起源，从而重新解释了136个畸变并发现了隐藏在正常染色体中的3个畸变。SKY确认了10个平衡畸变，并对G显带识别的3个平衡畸变进行了解释，并确定了另外9个平衡畸变，包括一个涉及RUNXI基因的新易位。G显带发现的32个缺失中有11个是隐性易位或插入，包括3个3号染色体缺失中的3个，3个del（7 q）中的2个，12个del（5 q）中的2个。在G显带完全丢失的92条染色体中，63条（68%）被证明涉及结构畸变。这对于-21（8例患者中的8例）、-5（6例患者中的5例）、-20（9例患者中的7例）和-18（12例患者中的6例）尤其如此。出乎意料的是，SKY在21例患者中发现了来自至少一条染色体的片段的隐藏的过度表达。最常见的是21 q，在8名患者中发现，其中4名患者具有高水平的21 q扩增。荧光原位杂交显示，RUNXI基因不是其中7例患者扩增的靶基因。此外，11 q（7名患者，包括3名高水平MLL基因扩增的患者）和22 q（7名患者）也经常增加。我们的结论是，SKY大大提高了核型解释的准确性，染色体材料的扩增可能发挥更大的作用，在白血病的发生比已经认识到的。(C)2002 Wiley-Liss，Inc.
We used spectral karyotyping (SKY) to study 29 adults with acute myeloid leukemia and a complex karyotype containing one to nine abnormalities that were not fully identifiable by G-banding. SKY showed the origin of rings and unidentified material in unbalanced translocations in all cases and the origin of markers in most, allowing reinterpretation of 136 aberrations and discovery of three aberrations hidden in normal chromosomes. SKY confirmed 10 and refined the interpretation of three balanced aberrations recognized by G-banding and identified another nine balanced aberrations, including a novel translocation involving the RUNXI gene. Eleven of 32 deletions found by G-banding were shown to be cryptic translocations or insertions, including three of four chromosome 3 deletions, two of three del(7q), and two of 12 del(5q). Of the 92 chromosomes deemed lost entirely by G-banding, 63 (68%) were shown to be involved in structural aberrations. This was especially true for -21 (eight of eight patients), -5 (five of six patients), -20 (seven of nine patients), and -18 (six of 12 patients). Unexpectedly, SKY uncovered a hidden overrepresentation of segments from at least one chromosome in 2 1 patients. The most frequently overrepresented was 21q, found in eight patients, including four with high-level 21q amplification. Fluorescence in situ hybridization showed that the RUNXI gene was not the target of amplification in seven of these patients. Also frequently gained were 11q (in seven patients, including three with high-level MLL gene amplification) and 22q (in seven patients). We conclude that SKY considerably enhances the accuracy of karyotype interpretation, and that amplification of chromosomal material may play a greater role in leukemogenesis than has been recognized. (C) 2002 Wiley-Liss, Inc.