Al Abri Yusra, Al Huneini Mohammed, Al Zadjali Shoaib, Al Rawahi Mohammed
Hematopathology Residency Training Program, Oman Medical Specialty Board, Muscat, Oman.
Hematology Department, Sultan Qaboos University Hospital, Muscat, Oman.
Oman Med J. 2024 Jan 31;39(1):e592. doi: 10.5001/omj.2023.126. eCollection 2024 Jan.
We sought to define the prevalence of isocitrate dehydrogenase (IDH) mutations, evaluate the clinicopathologic impact of IDH mutations, assess the effect of IDH mutations on the response to the currently offered treatment for acute myeloid leukemia (AML) cases, and determine the impact of other common concurrent mutations with IDH.
A single-center retrospective cohort study was conducted at Sultan Qaboos University Hospital (SQUH) from October 2009 to October 2019. We included all Omani patients (pediatric and adult) treated at SQUH with the standard therapy, for whom DNA extraction was performed at diagnosis. The target mutations in both IDH1 and IDH2 genes were screened using the direct polymerase chain reaction product sequencing method. Statistical analysis was conducted using SPSS software. Survival differences were estimated using the log-rank test. Continuous variables were presented as median (IQRs), while categorical variables were presented as frequency.
A total of 61 patients treated, for whom DNA extraction was performed at diagnosis were evaluated. The median age was 40 (range = 25.5-65.5). The prevalence of IDH1 R132, IDH2 R140, and IDH2 R172 mutations among the study group was 6.6%, 3.3%, and 1.6%, respectively. Clinicopathologic characteristics associated with IDH mutations at diagnosis included older age, lower white blood cell count, higher median platelet counts, normal karyotype AML, and cytogenetics intermediate-risk group. The overall survival (OS) in patients harboring IDH mutations was poor, with a median OS of nine months. This analysis confirms that the response rate and OS for both IDH-mutated and IDH wild-type AML patients were comparable. This will provide contemporary data to be used for comparison with the results of novel investigational (e.g., selective IDH inhibitor) strategies.
The current study results were consistent with the other international studies of IDH mutations in AML and demonstrate the poor prognosis associated with IDH mutations. Clinicopathologic features associated with IDH mutations included older age, lower white blood cell count, higher median platelet counts, normal karyotype AML, and cytogenetics intermediate-risk group.
我们试图确定异柠檬酸脱氢酶（IDH）突变的发生率，评估IDH突变对临床病理的影响，评估IDH突变对急性髓系白血病（AML）病例当前所提供治疗反应的影响，并确定与IDH同时存在的其他常见突变的影响。
2009年10月至2019年10月在苏丹卡布斯大学医院（SQUH）进行了一项单中心回顾性队列研究。我们纳入了所有在SQUH接受标准治疗的阿曼患者（儿童和成人），这些患者在诊断时进行了DNA提取。使用直接聚合酶链反应产物测序方法筛查IDH1和IDH2基因中的目标突变。使用SPSS软件进行统计分析。使用对数秩检验估计生存差异。连续变量以中位数（四分位间距）表示，分类变量以频率表示。
共评估了61例在诊断时进行了DNA提取的治疗患者。中位年龄为40岁（范围=25.5-65.5岁）。研究组中IDH1 R132、IDH2 R140和IDH2 R172突变的发生率分别为6.6%、3.3%和1.6%。诊断时与IDH突变相关的临床病理特征包括年龄较大、白细胞计数较低、中位血小板计数较高、核型正常的AML以及细胞遗传学中危组。携带IDH突变患者的总生存期（OS）较差，中位OS为9个月。该分析证实，IDH突变型和IDH野生型AML患者的缓解率和OS具有可比性。这将提供当代数据，用于与新型研究策略（如选择性IDH抑制剂）的结果进行比较。
当前研究结果与其他关于AML中IDH突变的国际研究一致，并证明了与IDH突变相关的不良预后。与IDH突变相关的临床病理特征包括年龄较大、白细胞计数较低、中位血小板计数较高、核型正常的AML以及细胞遗传学中危组。
