Elsayed Ghada M, Nassar Hanan R, Zaher Amr, Elnoshokaty Essam H, Moneer Manar M
Department of Clinical Pathology, National Cancer Institute, Cairo University, Egypt.
Department Medical Oncology, National Cancer Institute, Cairo University, Egypt.
J Egypt Natl Canc Inst. 2014 Mar;26(1):43-9. doi: 10.1016/j.jnci.2013.11.001. Epub 2013 Nov 27.
Somatic mutations in isocitrate dehydrogenase 1 (IDH1) gene occur frequently in primary brain tumors. Recently theses mutations were demonstrated in acute myeloid leukemia (AML). So far, assessment of these mutations relied on the DNA sequencing technique.
The aim of this study was to detect somatic mutations in IDH1 gene using mismatched primers suitable for endonuclease based detection, without the need for DNA sequencing, and to estimate its prognostic value, on patients with de novo AML.
Residual DNA extracted from pretreatment bone marrow (BM) samples of 100 patients with de novo AML was used. The polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was adapted to IDH1gene, codon 132 mutations screening.
The frequency of IDH1 mutations was 13%. In the non-acute promyelocytic leukemia group (non-APL), IDH1 mutations were significantly associated with FLT3-ITD negative patients (p=0.03). Patients with IDH1 mutations did not achieve complete remission (CR). There was a trend for shorter overall survival (OS) in patients with IDH1 mutation compared to those with wild type (p=0.08).
IDH1 mutations are recurring genetic alterations in AML and they may have unfavorable impact on clinical outcome in adult AML. The PCR-RFLP method allows for a fast, inexpensive, and sensitive method for the detection of IDH1 mutations in AML.
异柠檬酸脱氢酶1（IDH1）基因的体细胞突变在原发性脑肿瘤中频繁发生。最近，这些突变在急性髓系白血病（AML）中也得到了证实。到目前为止，这些突变的评估依赖于DNA测序技术。
本研究的目的是使用适合基于核酸内切酶检测的错配引物检测IDH1基因中的体细胞突变，无需DNA测序，并评估其对初发AML患者的预后价值。
使用从100例初发AML患者预处理骨髓（BM）样本中提取的残留DNA。聚合酶链反应-限制性片段长度多态性方法（PCR-RFLP）用于IDH1基因第132密码子突变的筛查。
IDH1突变频率为13%。在非急性早幼粒细胞白血病组（非APL）中，IDH1突变与FLT3-ITD阴性患者显著相关（p = 0.03）。IDH1突变患者未达到完全缓解（CR）。与野生型患者相比，IDH1突变患者的总生存期（OS）有缩短趋势（p = 0.08）。
IDH1突变是AML中反复出现的基因改变，可能对成人AML的临床结局产生不利影响。PCR-RFLP方法为检测AML中的IDH1突变提供了一种快速、廉价且灵敏的方法。
