Shuang Li1, Rong Fan2, Xiao-Li Zhao3, Xiao-Qin Wang4. 1. Department of Hematology, Huashan Hospital of Fudan University, Shanghai, China; Evidence-Based Medicine Center of Fudan University, Shanghai, China. 2. Department of Hematology, Changzheng Hospital of The Second Military Medical University, Shanghai, China. 3. Department of Hematology, Huashan Hospital of Fudan University, Shanghai, China. 4. Department of Hematology, Huashan Hospital of Fudan University, Shanghai, China; Evidence-Based Medicine Center of Fudan University, Shanghai, China. Electronic address: wangxiaoqin@shmu.edu.cn.
Abstract
OBJECTIVE: The CXXC domain protein 4 (CXXC4) functions as a negative regulator of Wnt signaling and also regulates expression of the ten-eleven translocation 2 (TET2) protein for DNA methylation. This study detected levels of CXXC4 and TET2 mRNA to determine their association with survival of patients with myelodysplastic syndrome (MDS). METHODS: Levels of TET2 and CXXC4 mRNA were analyzed in bone marrow samples from 154 MDS patients and 50 control subjects using qRT-PCR and subsequently associated these levels with clinicopathological characteristics and survival of MDS patients. RESULTS: Levels of TET2 and CXXC4 mRNA were significantly lower in MDS patients than that in controls (P=0.009 and P<0.001, respectively). Patients with advanced WHO subtypes (e.g., RAEB-1 and RAEB-2) exhibited a higher level of CXXC4 mRNA (P=0.020) compared to those with early stage subtypes (i.e., RA, RARS, RCMD, RCMD-RS, 5q-syndrome, and MDS-U). Moreover, levels of CXXC4 mRNA were associated with marrow blast levels (P=0.014) and neutrophil counts (P=0.039). Levels of CXXC4 mRNA and hemoglobin and IPSS cytopenias were associated with the overall survival (P=0.025) but not with the leukemia-free survival of MDS patients. The multivariate analysis demonstrated that the age of patients and levels of hemoglobin and marrow blast were independent risk factors for survival of MDS patients. CONCLUSION: This study demonstrated that the age of patients and levels of CXXC4 mRNA, hemoglobin, and marrow blast associated with survival of MDS patients.
OBJECTIVE: The CXXC domain protein 4 (CXXC4) functions as a negative regulator of Wnt signaling and also regulates expression of the ten-eleven translocation 2 (TET2) protein for DNA methylation. This study detected levels of CXXC4 and TET2 mRNA to determine their association with survival of patients with myelodysplastic syndrome (MDS). METHODS: Levels of TET2 and CXXC4 mRNA were analyzed in bone marrow samples from 154 MDSpatients and 50 control subjects using qRT-PCR and subsequently associated these levels with clinicopathological characteristics and survival of MDSpatients. RESULTS: Levels of TET2 and CXXC4 mRNA were significantly lower in MDSpatients than that in controls (P=0.009 and P<0.001, respectively). Patients with advanced WHO subtypes (e.g., RAEB-1 and RAEB-2) exhibited a higher level of CXXC4 mRNA (P=0.020) compared to those with early stage subtypes (i.e., RA, RARS, RCMD, RCMD-RS, 5q-syndrome, and MDS-U). Moreover, levels of CXXC4 mRNA were associated with marrow blast levels (P=0.014) and neutrophil counts (P=0.039). Levels of CXXC4 mRNA and hemoglobin and IPSS cytopenias were associated with the overall survival (P=0.025) but not with the leukemia-free survival of MDSpatients. The multivariate analysis demonstrated that the age of patients and levels of hemoglobin and marrow blast were independent risk factors for survival of MDSpatients. CONCLUSION: This study demonstrated that the age of patients and levels of CXXC4 mRNA, hemoglobin, and marrow blast associated with survival of MDSpatients.