ALL-1 GENE REARRANGEMENTS IN DNA TOPOISOMERASE-II INHIBITOR-RELATED LEUKEMIA IN CHILDREN
ALL-1 GENE REARRANGEMENTS IN DNA TOPOISOMERASE-II INHIBITOR-RELATED LEUKEMIA IN CHILDREN
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DOI：
10.1182/blood.v85.11.3250.bloodjournal85113250
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发表时间：
1995-06-01
期刊：
影响因子：
20.3
通讯作者：
LANGE, BJ
中科院分区：
文献类型：
--
作者：
FELIX, CA;HOSLER, MR;LANGE, BJ
我们研究了17例继发性白血病的临床、形态和细胞遗传学特征以及ALL-1(MLL、Htrx1、HRX)基因重排，这些患者发生在接受拓扑异构酶II抑制剂治疗的儿童原发癌症的11个月至9年后，或发展为与这种治疗相关的典型的继发性白血病。10例继发性白血病为急性髓系白血病(AML)，1例为混合家系，2例为急性淋巴细胞白血病(ALL)，4例表现为骨髓发育不良。在15例受累于11q23的白血病中，11例(73%)可被细胞遗传学鉴定：4例仅有分子重排，Southern印迹显示ALL-1基因重排与散发病例相似。(2)继发性11q23白血病的暴露史各不相同，其中1例仅用放线菌素作为拓扑异构酶II抑制剂，另1例未用过拓扑异构酶II抑制剂。(3)儿童继发性11q23白血病在临床、形态、细胞遗传学和分子水平上存在异质性。(4)儿童继发性11q23白血病虽有部分存活者，但其预后往往是致命的。(C)1995年由美国血液病学会主办。
We examined clinical, morphologic, and cytogenetic features and ALL-1 (MLL, Htrxl, HRX) gene rearrangements in 17 cases of secondary leukemia that occurred 11 months to 9 years from diagnoses of primary cancers in children who received topoisomerase II inhibitors or developed secondary leukemias typical of those associated with this therapy, Primary diagnoses included nine solid tumors and eight leukemias. Ten secondary leukemias were acute myeloid leukemia (AML), one was of mixed lineage, two were acute lymphoblastic leukemia (ALL), and four presented as myelodysplasia, Of 15 cases with 11q23 involvement, 11 (73%) were cytogenetically identifiable: four cases had molecular rearrangement only, By Southern blot, rearrangements within the ALL-1 gene were similar to sporadic cases, The results of this analysis suggest the following: (1) In most pediatric cases of topoisomerase II inhibitor-associated leukemia, there is disruption of the breakpoint cluster region of the ALL-1 gene at chromosomal band 11q23. (2) Exposure histories vary in secondary 11q23 leukemia, as the only topoisomerase II inhibitor was dactinomycin in one case, and, in another case, no topoisomerase II inhibitor was administered. (3) There is clinical, morphologic, cytogenetic, and molecular heterogeneity in pediatric secondary 11q23 leukemia, (4) There are some survivors of pediatric secondary 11q23 leukemia, but the outcome is most often fatal. (C) 1995 by The American Society of Hematology.