Felix C A, Hosler M R, Slater D J, Parker R I, Masterson M, Whitlock J A, Rebbeck T R, Nowell P C, Lange B J
Division of Oncology, The Children's Hospital of Philadelphia, Pennsylvania 19104-4318, USA.
J Pediatr Hematol Oncol. 1998 Jul-Aug;20(4):299-308. doi: 10.1097/00043426-199807000-00004.
To assess translocation breakpoint distribution within the MLL genomic breakpoint cluster region (bcr), 40 cases of de novo leukemia in children were examined by karyotype and Southern blot analysis.
Criteria for inclusion were karyotypic or molecular rearrangement of chromosome band 11q23. Of the 40 cases, 31 occurred in infants. Twenty cases were acute lymphoblastic leukemia (ALL), 17 were acute myeloid leukemia (AML), and 3 were biphenotypic.
Karyotype identified 27 cases with translocation of chromosome band 11q23 and 2 with abnormalities of band 11q13 but not 11q23. Southern blot analysis showed rearrangement within the MLL genomic bcr in 38 of the 40 cases. In these 38, additional probe-restriction digest combinations localized MLL genomic breakpoints to the 5' portion of the bcr in 14 cases and to the 3' portion in 18; material was insufficient for further localization to 5' or 3' within the bcr in 6 cases. In the two remaining cases, both with t(4;11)(q21;q23), one breakpoint mapped 5' of the bcr between intron 3 and exon 5, whereas the other breakpoint was neither within nor 5' of the MLL genomic bcr.
Suggested trends warranting investigation in more patients were breakpoint sites in the 3' bcr in AML and in patients older than 12 months. The distribution of MLL genomic breakpoints within the bcr in de novo leukemia in children is distinct from that in adults, where the breakpoints cluster in the 5' portion of the bcr.
为评估MLL基因组断裂点簇区域（bcr）内的易位断裂点分布情况，对40例儿童新发白血病患者进行了核型分析和Southern印迹分析。
纳入标准为染色体带11q23的核型或分子重排。40例患者中，31例为婴儿。20例为急性淋巴细胞白血病（ALL），17例为急性髓细胞白血病（AML），3例为双表型白血病。
核型分析鉴定出27例染色体带11q23易位，2例为11q13带异常但非11q23。Southern印迹分析显示40例中的38例在MLL基因组bcr内有重排。在这38例中，额外的探针 - 限制性酶切消化组合将MLL基因组断裂点定位到bcr的5'部分14例，3'部分18例；6例材料不足以进一步定位到bcr内的5'或3'。其余2例均为t(4;11)(q21;q23)，一个断裂点位于bcr的5'，在第3内含子和第5外显子之间，而另一个断裂点既不在MLL基因组bcr内，也不在其5'端。
值得在更多患者中研究的趋势包括AML以及12个月以上患者中3'bcr的断裂点位置。儿童新发白血病中MLL基因组断裂点在bcr内的分布与成人不同，成人的断裂点聚集在bcr的5'部分。
