Mahgoub N, Parker R I, Hosler M R, Close P, Winick N J, Masterson M, Shannon K M, Felix C A
Department of Pediatrics, University of California, San Francisco, USA.
Genes Chromosomes Cancer. 1998 Mar;21(3):270-5.
Translocations of the MLL gene at chromosome band 11q23 are the most common cytogenetic alterations in de novo leukemia in infants and in leukemia related to chemotherapy with DNA topoisomerase II inhibitors. Experiments on knock-in mice suggest that additional mutational events may by required for full leukemogenesis. Therefore, we used single-strand conformation polymorphism analysis and an allele-specific restriction enzyme assay to investigate the frequency of KRAS and NRAS mutations in 32 pediatric leukemias with translocation of the MLL gene. Of 25 de novo cases, 13 were acute lymphoblastic leukemia (ALL), 10 were acute myeloid leukemia (AML), and 2 were biphenotypic. Three secondary leukemias were AML, 1 was biphenotypic, 1 was ALL, and 2 were diagnosed as myelodysplasia. The frequency of RAS mutations was 2 of 10 in de novo AML. Both mutations occurred in infant monoblastic variants. RAS mutations were otherwise absent in this series. This is the first report of congenital leukemias where translocation of the MLL gene and RAS mutation coexist. The frequency of RAS mutations in de novo AMLs with MLL gene translocations is similar to that in other forms of AML, but RAS mutations play a limited role in lymphoid and treatment-related leukemias with similar translocations.
位于染色体11q23带的MLL基因易位是婴儿原发性白血病以及与DNA拓扑异构酶II抑制剂化疗相关白血病中最常见的细胞遗传学改变。对基因敲入小鼠的实验表明，完全白血病发生可能还需要其他突变事件。因此，我们使用单链构象多态性分析和等位基因特异性限制酶分析，来研究32例伴有MLL基因易位的儿童白血病中KRAS和NRAS突变的频率。在25例原发性病例中，13例为急性淋巴细胞白血病（ALL），10例为急性髓细胞白血病（AML），2例为双表型。3例继发性白血病为AML，1例为双表型，1例为ALL，2例被诊断为骨髓发育异常。原发性AML中RAS突变的频率为10例中有2例。这两个突变均发生在婴儿单核细胞变异型中。该系列中其他情况未出现RAS突变。这是关于MLL基因易位与RAS突变共存的先天性白血病的首次报道。伴有MLL基因易位的原发性AML中RAS突变的频率与其他形式的AML相似，但RAS突变在具有相似易位的淋巴样白血病和治疗相关白血病中作用有限。
