Impact of iron overload by transfusion on survival and leukemia transformation of myelodysplastic syndromes in a single center of China.

INTRODUCTION: Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases which are prone to progress into acute myeloid leukemia (AML). Iron overload (IOL) caused by transfusion occurred in most MDS patients. But how IOL influences MDS progression has not been clarified yet. METHODS: Herein, we collected clinical data from 143 MDS patients to investigate the impacts of IOL on patients survival and AML transformation. RESULTS: We found that median survival time, 3-year survival rate, leukemia-free survival (LFS) time were significantly shorter in patients with IOL than those with non-iron overload (NIOL) (P = 0.040; P = 0.044; P = 0.037). Besides, IOL was more likely to be found in higher-risk subgroups (assessed by IPSS and WPSS) of MDS patients which also promoted 2-year AML transformation. Furthermore, the serum ferritin (SF) was significantly correlated with the overall survival (OS) of MDS patients (r = -0.311, P < 0.05). The concentrations of both intracellular iron and reactive oxygen species (ROS) in CD34+ cells of bone marrow were higher in the IOL group than the NIOL group, respectively (P = 0.0426; P = 0.0185). Moreover, ROS level was closely correlated with the percentage of bone marrow blasts (r = 0.7200, P = 0.0370). Collectively, IOL threatened the survival of MDS patients and promoted AML transformation. CONCLUSION: Elevated intracellular iron and ROS in CD34+ cells of bone marrow could accelerate the abnormal proliferation of blasts.

Iron overload may promote alteration of NK cells and hematopoietic stem/progenitor cells by JNK and P38 pathway in myelodysplastic syndromes.

The objective of the study was to examine levels of intracellular iron, reactive oxygen species (ROS) and the expression of JNK and p38MAPK in NK cells and hematopoietic stem/progenitor cells (HSPCs) in MDS patients, and explore potential mechanisms by which iron overload (IOL) promotes MDS progression. Thirty-four cases of MDS and six cases of AML transformed from MDS (MDS/AML) were included. HSPCs and NK cells were isolated by magnetic absorption cell sorting. We used flow cytometry to detect the levels of ROS and intracellular JNK and P38 in NK cells and HSPCs. Total RNA and protein were extracted from NK cells and CD34+ cells to examine the expression of JNK and p38MAPK using RT-PCR and Western blotting. Intracellular iron concentration was detected. Data were analyzed by SPSS 21 statistical software. Intracellular iron concentration and ROS were increased in both NK cells and HSPCs in MDS patients with iron overload (P < 0.05). MDS patients with iron overload had higher JNK expression and lower p38 expression in NK cells, and higher p38 expression in HSPCs compared with non-iron overload group. IOL may cause alterations in NK cells and HSPCs through the JNK and p38 pathways, and play a role in the transformation to AML from MDS.

Validation of EORTC QLQ-LC43 for Chinese patients with lung cancer.

OBJECTIVES: To test the validity, reliability and acceptability of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 43 (EORTC QLQ-LC43) for Chinese patients with lung cancer. MATERIALS AND METHODS: Patients from Tianjin Cancer Institution and Hospital with lung cancer were enrolled in this study. All were treated in Tianjin Cancer Institution and Hospital from December 2012 to April 2013. All participants self-administered the EORTC QLQ-LC43 and the Short Form 36 Health Survey (SF-36). The Karnofsky performance scale (KPS) was performed to evaluate scores. Reliability test of the questionnaires was based on Cronbach's α coefficients, Pearson correlation test and Kruskal-Wallis test. RESULTS: This study included 317 inpatients and outpatients. The Cronbach's α coefficients were >0.70 in all scales of the two questionnaires, except that of cognitive functioning. High correlations were found among the quality of life (QoL), physical functioning, role functioning, dyspnea, and KPS scores (r>0.40). Mild correlations were discovered among the rest of the items. Dividing the participants into three groups based on the KPS scores showed that QoL and functional scales scores progressively decreased and the symptom items scores progressively increased as KPS scores decreased. All inter-group differences were statistically significant (P<0.05). CONCLUSION: The EORTC QLQ-LC43 is a reliable and valid instrument in patients with lung cancer and is appropriate for measuring the QoL of Chinese patients.