Abstract
This study aimed to explore the correlation of kinesin family member 2A (KIF2A) expression with disease risk, clinical characteristics, and prognosis of acute myeloid leukemia (AML), and investigate the effect of KIF2A knockdown on AML cell activities in vitro. Bone marrow samples were collected from 176 AML patients and 40 healthy donors, and KIF2A expression was measured by real-time quantitative polymerase chain reaction. Treatment response, event-free survival (EFS), and overall survival (OS) were assessed in AML patients. In vitro, KIF2A expression in AML cell lines and CD34+ cells (from healthy donors) was measured, and the effect of KIF2A knockdown on AML cell proliferation and apoptosis in HL-60 and KG-1 cells was detected. KIF2A expression was greater in AML patients compared to healthy donors, and receiver operating characteristic curve indicated that KIF2A expression predicted increased AML risk (area under curve: 0.793 (95%CI: 0.724-0.826)). In AML patients, KIF2A expression positively correlated with white blood cells, monosomal karyotype, and high risk stratification. Furthermore, no correlation of KIF2A expression with complete remission or hematopoietic stem cell transplantation was found. Kaplan-Meier curves showed that KIF2A expression was negatively correlated with EFS and OS. In vitro experiments showed that KIF2A was overexpressed in AML cell lines (KG-1, HL-60, ME-1, and HT-93) compared to CD34+ cells, moreover, cell proliferation was reduced but apoptosis was increased by KIF2A knockdown in HL-60 and KG-1 cells. In conclusion, KIF2A showed potential to be a biomarker and treatment target in AML.
Highlights
Acute myeloid leukemia (AML), one of the most malignant hematopoietic system diseases, is characterized by abnormal proliferation, poor cell differentiation, and infiltration of bone marrow, peripheral blood, or other tissues [1,2]
kinesin family member 2A (KIF2A) expression in acute myeloid leukemia (AML) patients KIF2A expression was elevated in AML patients [2.480 (1.232–3.809)] compared to healthy controls [1.162 (0.515–1.878)] (Po0.001) (Figure 1A), and Receiver operating characteristic (ROC) curve showed that KIF2A expression was able to distinguish AML patients from healthy controls with area under curve (AUC) of 0.793 (95%CI: 0.724–0.826) (Figure 1B)
According to the analyses published on GEO database, we found two datasets that exhibited KIF2A expressions in AML patients and normal controls (Figure S1): in detail, one dataset showed that KIF2A expression was increased in the bone marrow samples of pediatric AML patients compared to that of normal controls (Figure S1A), and the other one showed that KIF2A expression was similar between the bone
Summary
Acute myeloid leukemia (AML), one of the most malignant hematopoietic system diseases, is characterized by abnormal proliferation, poor cell differentiation, and infiltration of bone marrow, peripheral blood, or other tissues [1,2]. Emerging evidence has suggested that biomarkers related to disease progression and prognosis would contribute to individualize therapy and improve prevention of aggressive disease or treatment outcomes in AML patients. A few studies have shown that KIF2A is overexpressed in tumor tissues and correlates with clinicopathological features in patients with some cancers (such as diffuse large B cell lymphoma (DLBCL), breast cancer, and lung squamous cell carcinoma) [7,8,9]. Some in vitro experiments have shown that KIF2A functions as a tumor oncogene in several cancer cell lines
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More From: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
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