Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment-related acute myeloid leukemia: Correlation with scaffold attachment regions and topoisomerase II consensus binding sites
Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment-related acute myeloid leukemia: Correlation with scaffold attachment regions and topoisomerase II consensus binding sites
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DOI：
10.1182/blood.v87.5.1912.bloodjournal8751912
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发表时间：
1996-03-01
期刊：
影响因子：
20.3
通讯作者：
Rowley, JD
中科院分区：
文献类型：
--
作者：
Broeker, PLS;Super, HG;Rowley, JD
涉及MLL的11 q23易位的一个主要未解决的问题是导致这些易位的染色体机制。我们在31例初发急性淋巴细胞白血病和急性髓细胞白血病（AML）患者和8例t-AML患者中定位了8.3kb BamHI断裂点簇区域内的断裂点。在31例初发白血病患者中，23例MLL断裂点定位于着丝粒半区，（4.57 kb）的断裂点簇区域，而在8个新发患者中的那些定位于端粒的一半（3.87 hb）。相比之下，只有两个t-AML断裂点映射在着丝粒的一半，而六个映射在端粒的一半。白血病初发断点分布差异具有统计学意义（P = 0.02）。其他人报告了初治患者和t-AML患者之间断点分布的相似差异。我们确定了一个低或弱亲和力的支架附着区（SAR）映射着丝粒的断点簇区域，和一个高亲和力的SAR映射内的端粒的一半断点簇区域。使用高严格的标准来定义在体外脊椎动物拓扑异构酶II（拓扑II）的共识网站，拓扑II网站映射相邻的端粒SAR，而六个映射内的SAR。因此，74%的白血病初发和25%的t-AML断裂点映射到两个SAR之间断裂点簇区域的着丝粒部分;相反，26%的白血病初发和75%的t-AML患者断裂点映射到断裂点簇区域的端粒部分，其包含端粒SAR和topo II位点。因此，MLL断裂点簇区域的染色质结构在确定断裂点的分布中可能是重要的。数据表明，导致易位的机制可能在初发白血病和t-AML中不同。(C)1996年，美国血液学会。
A major unresolved question for the 11q23 translocations involving MLL is the chromosomal mechanism(s) leading to these translocations. We have mapped breakpoints within the 8.3-kb BamHI breakpoint cluster region in 31 patients with acute lymphoblastic leukemia and acute myeloid leukemia (AML) de novo and in 8 t-AML patients, In 23 of 31 leukemia de novo patients, MLL breakpoints mapped to the centromeric half (4.57 kb) of the breakpoint cluster region, whereas those in eight de novo patients mapped to the telomeric half (3.87 hb). In contrast, only two t-AML breakpoints mapped in the centromeric half, whereas six mapped in the telomeric half. The difference in distribution of the leukemia de novo breakpoints is statistically significant (P = .02). A similar difference in distribution of breakpoints between de novo patients and t-AML patients has been reported by others. We identified a low- or weak-affinity scaffold attachment region (SAR) mapping just centromeric to the breakpoint cluster region, and a high-affinity SAR mapping within the telomeric half of the breakpoint cluster region. Using high stringency criteria to define in vitro vertebrate topoisomerase II (topo II) consensus sites, one topo II site mapped adjacent to the telomeric SAR, whereas six mapped within the SAR. Therefore, 74% of leukemia de novo and 25% of t-AML breakpoints map to the centromeric half of the breakpoint cluster region map between the two SARs; in contrast, 26% of the leukemia de novo and 75% of the t-AML patient breakpoints map to the telomeric half of the breakpoint cluster region that contains both the telomeric SAR and the topo II sites. Thus, the chromatin structure of the MLL breakpoint cluster region may be important in determining the distribution of the breakpoints. The data suggest that the mechanism(s) leading to translocations may differ in leukemia de novo and in t-AML. (C) 1996 by The American Society of Hematology.