Moassass Faten, Moualla Yahia, Al-Halabi Bassel, Khamis Atieh, Al-Achkar Walid
Department of Molecular Biology and Biotechnology, Human Genetics Division Atomic Energy Commission Damascus Syria.
Department of Laboratory Diagnosis Faculty of Pharmacy, Ministry of Higher Education Tishreen University Lattakia Syria.
Health Sci Rep. 2024 Dec 4;7(12):e70231. doi: 10.1002/hsr2.70231. eCollection 2024 Dec.
Nucleophosmin ) gene mutations occur in approximately 30%-35% of individuals with an initial diagnosis of acute myeloid leukemia (AML). Mutations in this gene have been reported in 50%-60% of AML patients with a normal karyotype. These mutations help to distinguish clinicopathological and molecular features, setting them apart as a unique subset within the heterogeneous landscape of AML. In the present study, we investigated the frequency and clinical impact of in 100 newly diagnosed adult Syrian patients with AML-normal karyotype (NK) using direct sequencing.
We analyzed 100 AML-NK patients using direct sequencing to assess the prevalence and clinical impact of mutations, as well as the co-occurrence of -ITD and mutations.
Our results revealed that the prevalence of was 22% among the patients; 86.4% of these mutations were type A (NM_002520.5:c.860-863dupTCTG), while 13.6% were de novo mutations (c.863_864insCCTG, p.Trp288CysfsTer12), (c.861_862dup, p.Trp288SerfsTer13), and (c.863_864insCCGG, p.Trp288CysfsTer12). Among our patients, 22% exhibited , with 7% also harboring and 2% having . The presence of was correlated with a statistically significant increase in bone marrow blast percentage ( = 0.017). Notably, patients with displayed significantly higher mortality rates, with 72.7% succumbing to the disease compared to 29.5% of patients without ( < 0.001). Furthermore, our results showed that when the overall survival (OS) time exceeded 8.35 months, the likelihood of wild-type status was greater.
The evaluation of and co-mutation has consistently demonstrated remarkable prognostic significance in AML, suggesting the potential for improved response rates, extended disease-free periods, and OS. Our findings provide valuable insights for understanding molecular leukemogenesis in AML-NK patients and will aid in clinical diagnosis, prognostic implications, and the development of targeted therapy strategies for Syrian AML patients.
核仁磷酸蛋白（NPM1）基因突变发生在约30%-35%初诊为急性髓系白血病（AML）的患者中。在50%-60%核型正常的AML患者中报告了该基因突变。这些突变有助于区分临床病理和分子特征，使其在AML异质性格局中成为一个独特的亚组。在本研究中，我们采用直接测序法调查了100例新诊断的核型正常的成年叙利亚AML患者中NPM1的突变频率及其临床影响。
我们采用直接测序法分析100例AML-NK患者，以评估NPM1突变的发生率及其临床影响，以及NPM1内部串联重复（NPM1-ITD）与NPM1突变的共发生情况。
我们的结果显示，患者中NPM1突变的发生率为22%；这些突变中86.4%为A型（NM_002520.5:c.860-863dupTCTG），而13.6%为新发突变（c.863_864insCCTG，p.Trp288CysfsTer12）、（c.861_862dup，p.Trp288SerfsTer13）和（c.863_864insCCGG，p.Trp288CysfsTer12）。在我们的患者中，22%表现出NPM1突变，其中7%同时存在NPM1-ITD，2%存在其他突变。NPM1突变的存在与骨髓原始细胞百分比的统计学显著增加相关（P=0.017）。值得注意的是，NPM1突变患者的死亡率显著更高，72.7%的患者死于该疾病，而无NPM1突变的患者为29.5%（P<0.001）。此外，我们的结果表明，当总生存（OS）时间超过8.35个月时，NPM1野生型状态的可能性更大。
对NPM1及其共突变的评估在AML中一直显示出显著的预后意义，提示可能提高缓解率、延长无病生存期和总生存期。我们的研究结果为理解AML-NK患者的分子白血病发生提供了有价值的见解，并将有助于叙利亚AML患者的临床诊断、预后评估及靶向治疗策略的制定。
