Bhattacharyya Jina, Nath Sukanta, Saikia Kandarpa Kumar, Saxena Renu, Sazawal Sudha, Barman Manash Pratim, Kumar Dushyant
1Department of Clinical Haematology, Gauhati Medical College and Hospital, Guwahati, Assam India.
2Department of Bioengineering and Technology, Gauhati University, Guwahati, Assam 781014 India.
Indian J Hematol Blood Transfus. 2018 Jan;34(1):32-42. doi: 10.1007/s12288-017-0821-0. Epub 2017 Apr 28.
Acute Myeloid Leukaemia (AML) is one of the common forms of haematological malignancy in adults. We analysed the prevalence and clinical significance of FMS-like tyrosine kinase 3 (FLT3) and Nucleophosmin 1 (NPM1) mutations in AML patients of North East India. Co-prevalence and clinical significance of three recurrent chromosomal translocations namely t(15; 17), t(8; 21), t(16; 16) and expression of epidermal growth factor receptor (EGFR), flow markers were also documented and co-related with disease progress. We analysed bone marrow aspirates or peripheral blood samples from 165 newly diagnosed AML patients. All clinical samples were analysed by Real Time PCR and DNA sequencing based assays. NPM1 was the most frequently detected mutation in the study population (46/165 = 27.90%, 95% CI 20.75-35.05). FLT3 mutations were detected in 27/165 (16.40%, 95% CI 10.45-22.35) patients with internal tandem duplication (FLT3-ITD) in 24/165 (14.60%, 95% CI 8.91-20.29) and FLT3-D835 in 3/165 (1.80%, 95% CI 0-4.13) patients. NPM1 mutations were associated with a higher complete remission rate and longer overall survival ( < 0.01) compared to FLT3-ITD whereas FLT3-ITD showed adverse impact with poor survival rate ( < 0.01), leukocytosis ( < 0.01) and a packed bone marrow. EGFR expression was more in patients with NPM1 mutation compared to FLT3 mutation ( = 0.09). Patients with FLT3 and NPM1 mutations uniformly expressed CD13 and CD33 whereas CD34 was associated with poor prognosis ( ≤ 0.01) in patients with NPM1 mutation. FLT3-ITD was associated with inferior overall survival. However the clinical significance of FLT3-D835 was not clear due to small number of samples. NPM1 mutation showed better prognosis with increased response to treatment in the absence of FLT3-ITD.
急性髓系白血病（AML）是成人血液系统恶性肿瘤的常见形式之一。我们分析了印度东北部AML患者中FMS样酪氨酸激酶3（FLT3）和核仁磷酸蛋白1（NPM1）突变的发生率及临床意义。还记录了三种常见染色体易位t(15; 17)、t(8; 21)、t(16; 16)的共发生率及临床意义，以及表皮生长因子受体（EGFR）的表达、流式细胞标志物，并将其与疾病进展进行关联分析。我们分析了165例新诊断AML患者的骨髓穿刺物或外周血样本。所有临床样本均通过实时荧光定量PCR和基于DNA测序的检测方法进行分析。NPM1是研究人群中最常检测到的突变（46/165 = 27.90%，95%置信区间20.75 - 35.05）。27/165（16.40%，95%置信区间10.45 - 22.35）例患者检测到FLT3突变，其中24/165（14.60%，95%置信区间8.91 - 20.29）例为内部串联重复（FLT3-ITD），3/165（1.80%，95%置信区间0 - 4.13）例为FLT3-D835。与FLT3-ITD相比，NPM1突变与更高的完全缓解率和更长的总生存期相关（P < 0.01），而FLT3-ITD对生存率差（P < 0.01）、白细胞增多（P < 0.01）和骨髓细胞密集有不良影响。与FLT3突变相比，NPM1突变患者的EGFR表达更高（P = 0.09）。FLT3和NPM1突变患者均一致表达CD13和CD33，而CD34与NPM1突变患者的不良预后相关（P ≤ 0.01）。FLT3-ITD与较差的总生存期相关。然而，由于样本量少，FLT3-D835的临床意义尚不清楚。在无FLT3-ITD的情况下，NPM1突变显示出对治疗反应增加且预后更好。
