Fischer K, Fröhling S, Scherer S W, McAllister Brown J, Scholl C, Stilgenbauer S, Tsui L C, Lichter P, Döhner H
Medizinische Klinik, University of Heidelberg, Germany.
Blood. 1997 Mar 15;89(6):2036-41.
Loss of chromosome 7 (-7) or deletion of its long arm (7q-) are recurring chromosome abnormalities in myeloid disorders, especially in therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML). The association of -7/7q- with myeloid leukemia suggests that these regions contain a novel tumor suppressor gene(s) whose loss of function contributes to leukemic transformation or tumor progression. Based on chromosome banding analysis, two critical regions have been identified: one in band 7q22 and a second in bands 7q32-q35. We analyzed bone marrow and blood samples from 21 patients with myeloid leukemia (chronic myeloid leukemia, n = 2; de novo MDS, n = 4; de novo AML, n = 13; t-AML, n = 2) that on chromosome banding analysis exhibited deletions (n = 19) or reciprocal translocations (n = 2) of band 7q22 using fluorescence in situ hybridization. As probes, we used Alu-polymerase chain reaction products from 22 yeast artificial chromosome (YAC) clones that span chromosome bands 7q21.1-q32, including representative clones from a panel of YACs recognizing a contiguous genomic DNA fragment of 5 to 6 Mb in band 7q22. In the 19 cases with deletions, we identified two distinct commonly deleted regions: one region within band 7q22 was defined by the two CML cases; the second region encompassed a distal part of band 7q22 and the entire band 7q31 and was defined by the MDS/AML cases. The breakpoint of one of the reciprocal translocations was mapped to 7q21.3, which is centromeric to both of the commonly deleted regions. The breakpoint of the second translocation, which was present in unstimulated bone marrow and phytohemagglutinin-stimulated blood of an MDS patient, was localized to a 400-kb genomic segment in 7q22 within the deletion cluster of the MDS/AML cases. In conclusion, our data show marked heterogeneity of 7q22 deletion and translocation breakpoints in myeloid leukemias, suggesting the existence of more than one pathogenetically relevant gene.
7号染色体缺失（-7）或其长臂缺失（7q-）是髓系疾病中反复出现的染色体异常，尤其是在治疗相关的骨髓增生异常综合征（t-MDS）和急性髓系白血病（t-AML）中。-7/7q-与髓系白血病的关联表明，这些区域含有一个新的肿瘤抑制基因，其功能丧失促进白血病转化或肿瘤进展。基于染色体带型分析，已确定两个关键区域：一个在7q22带，另一个在7q32-q35带。我们使用荧光原位杂交分析了21例髓系白血病患者（慢性髓系白血病，n = 2；原发性骨髓增生异常综合征，n = 4；原发性急性髓系白血病，n = 13；t-AML，n = 2）的骨髓和血液样本，这些样本在染色体带型分析中显示7q22带的缺失（n = 19）或相互易位（n = 2）。作为探针，我们使用了来自22个酵母人工染色体（YAC）克隆的Alu聚合酶链反应产物，这些克隆跨越7q21.1-q32染色体带，包括一组YAC中识别7q22带中5至6 Mb连续基因组DNA片段的代表性克隆。在19例缺失病例中，我们确定了两个不同的常见缺失区域：7q22带内的一个区域由2例慢性髓系白血病病例确定；第二个区域包括7q22带的远端部分和整个7q31带，由骨髓增生异常综合征/急性髓系白血病病例确定。其中一个相互易位的断点定位于7q21.3，它位于两个常见缺失区域的着丝粒侧。第二个易位的断点存在于一名骨髓增生异常综合征患者未受刺激的骨髓和植物血凝素刺激的血液中，定位于7q22中400 kb的基因组片段，该片段位于骨髓增生异常综合征/急性髓系白血病病例的缺失簇内。总之，我们的数据显示髓系白血病中7q22缺失和易位断点存在明显的异质性，提示存在不止一个与发病机制相关的基因。
