National Specialized Hospital for Active Treatment of Hematological Diseases, Laboratory of Cytogenetics and Molecular Biology, Sofia, Bulgaria ; Center of Excellence for Translational Research in Hematology, Sofia, Bulgaria.
Center of Excellence for Translational Research in Hematology, Sofia, Bulgaria ; National Specialized Hospital for Active Treatment of Hematological Diseases, Hematology Clinic, Sofia, Bulgaria.
Turk J Haematol. 2014 Mar;31(1):40-8. doi: 10.4274/Tjh.2013.0023. Epub 2014 Mar 5.
Mutations of the nucleophosmin (NPM1) gene are considered as the most frequent acute myeloid leukemia (AML)-associated genetic lesion, reported with various incidences in different studies, and type A (NPM1-A) is the most frequent type. However, since most series in the literature report on the features of all patients regardless of the type of mutation, NPM1-A(+) cases have not been well characterized yet. Therefore, we evaluated the prevalence of NPM1-A in Bulgarian AML patients and searched for an association with clinical and laboratory features.
One hundred and four adults (51 men, 53 women) were included in the study. NPM1-A status was determined using allele-specific reverse-transcription polymerase chain reaction with co-amplification of NPM1-A and β-actin and real-time quantitative TaqMan-based polymerase chain reaction. Patients received conventional induction chemotherapy and were followed for 13.2±16.4 months.
NPM1-A was detected in 26 (24.8%) patients. NPM1-A mutation was detected in all AML categories, including in one patient with RUNX1-RUNX1T1. There were no differences associated with the NPM1-A status with respect to age, sex, hemoglobin, platelet counts, percentage of bone marrow blasts, splenomegaly, complete remission rates, and overall survival. NPM1-A(+) patients, compared to NPM1-A(-) patients, were characterized by higher leukocyte counts [(75.4±81.9)x109/L vs. (42.5±65.9)x109/L; p=0.049], higher frequency of normal karyotype [14/18 (77.8%) vs. 26/62 (41.9%); p=0.014], higher frequency of FLT3-ITD [11/26 (42.3%) vs. 8/77 (10.4%); p=0.001], and lower incidence of CD34(+) [6/21 (28.8%) vs. 28/45 (62.2%); p=0.017]. Within the FLT3-ITD(-) group, the median overall survival of NPM1-A(-) patients was 14 months, while NPM1-A(+) patients did not reach the median (p=0.10).
The prevalence of NPM1-A mutation in adult Bulgarian AML patients was similar to that reported in other studies. NPM1-A(+) patients were characterized by higher leukocyte counts, higher frequency of normal karyotypes and FLT3-ITD, and lower incidence of CD34(+), supporting the idea that the specific features of type A mutations might contribute to the general clinical and laboratory profile of NPM1(+) AML patients.
核磷蛋白（NPM1）基因突变被认为是最常见的急性髓系白血病（AML）相关遗传病变，在不同的研究中有不同的发生率，A 型（NPM1-A）是最常见的类型。然而，由于文献中的大多数系列报告了所有患者的特征，而不论突变类型如何，因此尚未对 NPM1-A（+）病例进行很好的描述。因此，我们评估了保加利亚 AML 患者中 NPM1-A 的流行情况，并研究了其与临床和实验室特征的关联。
本研究纳入了 104 名成年人（51 名男性，53 名女性）。使用等位基因特异性逆转录聚合酶链反应（PCR）结合 NPM1-A 和 β-肌动蛋白的共扩增以及实时定量 TaqMan-PCR 来确定 NPM1-A 状态。患者接受常规诱导化疗，并随访 13.2±16.4 个月。
在 26 名（24.8%）患者中检测到 NPM1-A。NPM1-A 突变在所有 AML 类别中均有检测到，包括在一名 RUNX1-RUNX1T1 患者中。NPM1-A 状态与年龄、性别、血红蛋白、血小板计数、骨髓原始细胞百分比、脾肿大、完全缓解率和总生存率均无相关性。与 NPM1-A（-）患者相比，NPM1-A（+）患者的白细胞计数更高[(75.4±81.9)x109/L vs. (42.5±65.9)x109/L；p=0.049]，核型正常的频率更高[14/18（77.8%） vs. 26/62（41.9%）；p=0.014]，FLT3-ITD 的频率更高[11/26（42.3%） vs. 8/77（10.4%）；p=0.001]，CD34（+）的发生率更低[6/21（28.8%） vs. 28/45（62.2%）；p=0.017]。在 FLT3-ITD（-）组中，NPM1-A（-）患者的中位总生存期为 14 个月，而 NPM1-A（+）患者尚未达到中位生存期（p=0.10）。
在成年保加利亚 AML 患者中，NPM1-A 突变的流行率与其他研究报道的相似。NPM1-A（+）患者的白细胞计数更高，核型正常和 FLT3-ITD 的频率更高，CD34（+）的发生率更低，支持 A 型突变的特定特征可能有助于 NPM1（+）AML 患者的一般临床和实验室特征的观点。
