Byers Richard, Hornick Jason L, Tholouli Eleni, Kutok Jeffery, Rodig Scott J
School of Cancer and Enabling Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
Appl Immunohistochem Mol Morphol. 2012 Jan;20(1):37-40. doi: 10.1097/PAI.0b013e31822c132e.
IDH1 mutations are present but are uncommon in acute myeloid leukemia (AML) and although prognostically favorable in gliomas their clinical significance in AML is unclear. Some have associated IDH1 mutations with inferior outcome, whereas others found no association with prognosis. Complicating these analyses is the need to sequence IDH1 from leukemic blasts, which is technically challenging and not yet routine. Mutation-specific antibodies enable robust, cost-effective detection of mutations in routine biopsy samples. Immunohistochemistry for the R132H mutation-specific antibody was performed in a tissue microarray containing 159 cases of AML, detecting the R132H mutation in 7 cases (4.4%). Positivity was associated with intermediate risk cytogenetics. Our results demonstrate an association between the R132H IDH1 mutation and intermediate risk cytogenetics in AML, suggesting that R132H IDH1 mutation may be associated with improved clinical outcome and demonstrate the feasibility of using mutation-specific antibodies to genotype and subclassify AML.
异柠檬酸脱氢酶1（IDH1）突变在急性髓系白血病（AML）中存在但并不常见。虽然其在胶质瘤中预后良好，但其在AML中的临床意义尚不清楚。一些研究将IDH1突变与较差的预后相关联，而另一些研究则未发现其与预后有关。使这些分析复杂化的是需要对白血病原始细胞进行IDH1测序，这在技术上具有挑战性且尚未成为常规操作。突变特异性抗体能够在常规活检样本中对突变进行可靠且经济高效的检测。在一个包含159例AML病例的组织芯片上进行了针对R132H突变特异性抗体的免疫组织化学检测，在7例（4.4%）病例中检测到R132H突变。阳性与中等风险细胞遗传学相关。我们的结果表明AML中R132H IDH1突变与中等风险细胞遗传学之间存在关联，提示R132H IDH1突变可能与改善的临床结局相关，并证明了使用突变特异性抗体对AML进行基因分型和亚分类的可行性。
