Molecular characterization of AML with ins(21;8)(q22;q22q22) reveals similarity to t(8;21) AML. Homo sapiens

In acute myeloid leukemia (AML) non-random clonal chromosome aberrations are detectable in ~55% of adults with AML. Translocation t(8;21)(q22;q22) resulting in the 5'RUNX1/3'RUNX1T1 fusion gene occurs in ~8% of acute myeloid leukemia (AML) cases. Also, insertions ins(8;21) and ins(21;8) have been described that show a broad heterogeneity at the molecular level with inserted fragment sizes ranging from 2.4 to 44 Mb. Microarray-based comparative genomic hybridization (arrayCGH) in 49 intermediate-risk AML and RT-PCR-based screening in 532 AML cases allowed the detection of ins(21;8)/ins(8;21) in three cases; arrayCGH and subsequent RT-PCR revealed an ~0.5 Mb sized inserted fragment generating the 5'RUNX1/3'RUNX1T1 fusion gene in one case with a submicroscopic ins(21;8)(q22;q22q22) whereas the other two cases were identified by banding analysis and RT-PCR, respectively. Gene expression profiling (GEP) and a detailed review of the literature highlighted similar biological features of AML cases with ins(21;8)/ins(8;21) and t(8;21)(q22;q22). Our study demonstrates the potential of high-resolution array-based analysis and GEP and provides further evidence that AML with insertions generating the 5'RUNX1/3'RUNX1T1 fusion not only biologically resemble the t(8;21)(q22;q22) AML subgroup, but might also share their prognostically favorable clinical behavior. Thus, similar treatment options should be considered in these patients. Overall design: An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract.

急性髓系白血病（acute myeloid leukemia, AML）患者中，约55%的成人可检出非随机性克隆染色体畸变。导致5'RUNX1/3'RUNX1T1融合基因形成的易位t(8;21)(q22;q22)，约见于8%的AML病例。此外，已有研究报道了插入型畸变ins(8;21)与ins(21;8)，此类畸变在分子层面呈现广泛异质性，插入片段长度介于2.4 Mb至44 Mb之间。本研究对49例中危AML患者开展基于微阵列的比较基因组杂交（microarray-based comparative genomic hybridization, arrayCGH）检测，并对532例AML患者实施基于逆转录聚合酶链反应（reverse transcription polymerase chain reaction, RT-PCR）的筛查，最终在3例患者中检出ins(21;8)/ins(8;21)。其中，1例存在亚显微级ins(21;8)(q22;q22q22)的患者，经arrayCGH联合后续RT-PCR检测发现，其插入片段长度约为0.5 Mb，可形成5'RUNX1/3'RUNX1T1融合基因；另外2例则分别通过核型分析与RT-PCR得以确诊。基因表达谱分析（gene expression profiling, GEP）结合详细的文献复习结果显示，携带ins(21;8)/ins(8;21)与t(8;21)(q22;q22)的AML患者具有相似的生物学特征。本研究证实了高分辨率阵列分析与GEP的应用潜力，并进一步证明：携带可生成5'RUNX1/3'RUNX1T1融合基因的插入型畸变的AML，不仅在生物学特征上与t(8;21)(q22;q22)型AML亚型高度相似，其临床预后也同样良好。因此，此类患者应考虑采用与该亚型一致的治疗方案。实验整体设计：采用全配对实验设计方案，即所有标记提取物之间均进行两两比对。