Dawson Angelika J, Bal Shibani, McTavish Barry, Tomiuk Michelle, Schroedter Ingo, Ahsanuddin Arshad N, Seftel Matthew D, Vallente Rhea, Mai Sabine, Cotter Philip D, Hovanes Karine, Gorre Mercedes, Gunn Shelly R
Cytogenetic Laboratory, Diagnostic Services of Manitoba, Health Sciences Centre, Winnipeg, Canada.
Cancer Genet. 2011 Jun;204(6):344-7. doi: 10.1016/j.cancergen.2011.05.005.
Acute myelomonocytic leukemia with eosinophilia is commonly associated with pericentric inversions of chromosome 16, involving the core binding factor beta gene (CBFB) on 16q22 and the myosin heavy chain gene (MYH11) on 16p13. The inv(16)(p13q22) results in a fusion gene comprising the 5'CBFB gene and the 3'MYH11 gene on the short arm of chromosome 16. The fusion gene interferes with the normal transcription of the CBFA/CBFB heterodimer and disrupts myeloid differentiation. The inv(16) is associated with a good prognosis. The inv(16) with deletion of the 3'CBFB region of the gene is a very rare occurrence. Although the number of cases is small, inv(16) with a deleted 3'CBFB seems to be associated with a poorer prognosis than that generally associated with inv(16). Our patient was a 30-year-old man with newly diagnosed acute myeloid leukemia who was found to have a CBFB-MYH11 fusion by reverse transcriptase-polymerase chain reaction. The high blast count and lack of differentiation were not typical for this entity and suggested clonal progression. The initial karyotype by conventional cytogenetic analysis, in all metaphases examined, was 46,XY,del(7)(q32),del(16)(q22). Fluorescence in situ hybridization analysis with a dual-color, break-apart probe corresponding to the CBFB gene locus (Abbott, Des Plaines, IL) showed a derivative chromosome 16 resulting from an inversion of the CBFB gene with a deletion of the 3'CBFB probe region. Oligonucleotide array comparative genetic hybridization analysis was performed on this patient's diagnostic bone marrow DNA referenced to a normal male control DNA by using the DNAarray Heme Profile (CombiMatrix Diagnostics, Irvine, CA) microarray. This analysis showed a 1.2 Mb loss of 16q22.1, which did not include loss of the 3'CBFB gene locus, but rather sequences distal to this locus. The DNAarray Heme Profile results illustrate the importance of microarray in the correct identification of abnormalities that will affect prognosis.
伴有嗜酸性粒细胞增多的急性粒单核细胞白血病通常与16号染色体的臂间倒位有关，涉及16q22上的核心结合因子β基因（CBFB）和16p13上的肌球蛋白重链基因（MYH11）。inv(16)(p13q22)导致在16号染色体短臂上形成一个由5'CBFB基因和3'MYH11基因组成的融合基因。该融合基因干扰CBFA/CBFB异二聚体的正常转录并破坏髓系分化。inv(16)与良好的预后相关。基因3'CBFB区域缺失的inv(16)非常罕见。虽然病例数量较少，但3'CBFB缺失的inv(16)似乎比一般与inv(16)相关的预后更差。我们的患者是一名30岁新诊断的急性髓系白血病男性，通过逆转录聚合酶链反应发现其存在CBFB-MYH11融合。高原始细胞计数和缺乏分化并非该实体的典型表现，提示克隆进展。通过常规细胞遗传学分析，在所有检测的中期相中，初始核型为46,XY,del(7)(q32),del(16)(q22)。使用对应于CBFB基因座的双色断裂探针（雅培公司，伊利诺伊州德斯普兰斯）进行荧光原位杂交分析显示，一条衍生的16号染色体是由CBFB基因倒位并缺失3'CBFB探针区域导致的。对该患者诊断时的骨髓DNA进行寡核苷酸阵列比较基因组杂交分析，以正常男性对照DNA为参照，使用DNAarray Heme Profile（CombiMatrix诊断公司，加利福尼亚州欧文）微阵列。该分析显示16q22.1缺失1.2 Mb，这并不包括3'CBFB基因座的缺失，而是该基因座远端的序列。DNAarray Heme Profile结果说明了微阵列在正确识别影响预后的异常方面的重要性。
