The clinical implications of cohesin gene complex mutation in acute myeloid leukemia (AML) are not well characterized. In the present study, all participants were thoroughly analyzed for chromosomal aberrations by conventional and molecular cytogenetic analysis in a cohort of 152 de novo unselected adult AML patients. Further, we examined the frequency and clinical implications of mutations in cohesin gene complex STAG1, STAG2, RAD21, SMC1, and SMC3 using whole exome sequencing as a pilot study in 10 de novo patients with AML-FAB M2. Among the 10 cases, we identified a functionally heterozygous mutation in exon16 of STAG1 in one patient (10%), however no mutation was observed in STAG2, RAD21, SMC1, and SMC3. Sanger sequencing analysis for exon 16 of STAG1 in the remaining 142 AML cases did not reveal any further mutations, which underlined the fact that mutations took place throughout the cohesion gene complex were without presence of mutational hot spot region. Present study identified a positive correlation between serum bilirubin, LDH and hematological parameters like Hb, WBC and Platelet count with STAG1 mutation. Our data suggests that the cohesin complex may represent an attractive therapeutic target for future preclinical and clinical studies, however more studies with a larger number of patients should be performed prospectively to determine the pathogenic involvement of STAG 1 mutation in AML patients.

中文翻译：

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完整外显子组测序可确定从头开始的急性髓细胞性白血病（FAB M2）中的黏附素组分STAG1突变：具有细胞遗传学，临床和预后意义的先导研究

黏着蛋白基因复合物突变在急性髓细胞性白血病（AML）中的临床意义尚不清楚。在本研究中，通过常规和分子细胞遗传学分析对152名从未选择的成年AML患者进行了全面的染色体畸变分析。此外，我们使用全外显子组测序对10例AML-FAB M2新生患者进行了黏附素基因复合体STAG1，STAG2，RAD21，SMC1和SMC3突变的频率和临床意义的初步研究。在这10例病例中，我们在一名患者（10％）中发现了STAG1外显子16的功能性杂合突变，但是在STAG2，RAD21，SMC1和SMC3中未观察到突变。在其余142例AML病例中，STAG1外显子16的Sanger测序分析未发现任何进一步的突变，这突显了这样一个事实，即在整个内聚基因复合体中都发生了突变，而没有突变热点区域。目前的研究确定了血清胆红素，LDH与血液学参数如Hb，WBC和血小板计数与STAG1突变之间呈正相关。我们的数据表明，粘着蛋白复合物可能代表了未来的临床前和临床研究的有吸引力的治疗靶标，但是，应前瞻性地进行更多的针对更多患者的研究，以确定AML患者中STAG 1突变的致病性。具有STAG1突变的WBC和血小板计数。我们的数据表明，粘着蛋白复合物可能代表了未来的临床前和临床研究的有吸引力的治疗靶标，但是，应前瞻性地进行更多的针对更多患者的研究，以确定AML患者中STAG 1突变的致病性。具有STAG1突变的WBC和血小板计数。我们的数据表明，粘着蛋白复合物可能代表了未来的临床前和临床研究的有吸引力的治疗靶标，但是，应前瞻性地进行更多的针对更多患者的研究，以确定AML患者中STAG 1突变的致病性。