Abdellateif Mona S, Kassem Amira B, El-Meligui Yomna M
Medical Biochemistry and Molecular Biology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhur, Egypt.
Int J Gen Med. 2020 Oct 16;13:867-879. doi: 10.2147/IJGM.S276138. eCollection 2020.
Acute myeloid leukemia (AML) is a common hematological malignancy associated with different cytogenetic and genetic abnormalities.
FLT3-internal tandem duplication (FLT3/ITD) mutation and CD34 expression levels were assessed in the bone marrow (BM) aspirates of 153 de novo AML patients. Data were correlated with relevant clinic-pathological features of the patients, response to treatment, disease-free survival (DFS), and overall free survival (OS) rates.
FLT3-ITD mutation was detected in 27/153 (17.6%) AML patients (=0.001), and CD34 was expressed in 83/153 (54.2%) patients (=0.293) compared to those with wild FLT3 and CD34 expression, respectively. Patients with FLT3-ITD mutation showed increased peripheral blood and BM blast cells, abnormal cytogenetics, poor DFS and OS compared to those with wild FLT3 (=0.013, <0.001, =0.010, =0.008 and =0.004, respectively), while there was no significant association with response to treatment (=0.081). There was no significant association between CD34 expression and response to treatment, DFS, and OS (>0.05). FLT3-ITD mutation and FAB subtypes were independent prognostic factors for DFS. Older age ≥39 years, HB <7 mg/dL PB blast ≥54%, and FLT3-ITD mutation were independent prognostic factors for poor OS in AML patients. The presence of both FLT3-ITD mutation and CD34 expression associated significantly with resistance to therapy (=0.024), short DFS and OS rates (=0.006, =0.037, respectively).
Combined expression of both FLT3-ITD mutation and CD34 expression is an important prognostic and predictive factor for poor disease outcome in AML patients.
急性髓系白血病(AML)是一种常见的血液系统恶性肿瘤,与不同的细胞遗传学和基因异常相关。
对153例初治AML患者的骨髓穿刺液进行FLT3内部串联重复(FLT3/ITD)突变和CD34表达水平评估。数据与患者的相关临床病理特征、治疗反应、无病生存期(DFS)和总生存期(OS)率相关。
153例AML患者中有27例(17.6%)检测到FLT3-ITD突变(P=0.001),83例(54.2%)患者表达CD34(P=0.293),分别与野生型FLT3和CD34表达的患者相比。与野生型FLT3患者相比,FLT3-ITD突变患者的外周血和骨髓原始细胞增加、细胞遗传学异常、DFS和OS较差(分别为P=0.013、<0.001、P=0.010、P=0.008和P=0.004),而与治疗反应无显著相关性(P=0.081)。CD34表达与治疗反应、DFS和OS之间无显著相关性(P>0.05)。FLT3-ITD突变和FAB亚型是DFS的独立预后因素。年龄≥39岁、血红蛋白<7mg/dL、外周血原始细胞≥54%和FLT3-ITD突变是AML患者OS不良的独立预后因素。FLT3-ITD突变和CD34表达均存在与治疗耐药性显著相关(P=0.024),DFS和OS率较短(分别为P=0.006、P=0.037)。
FLT3-ITD突变和CD34表达的联合表达是AML患者疾病预后不良的重要预后和预测因素。