GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines

BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ANKRD26.However,the positive regulators of ANKRD26 are still unknown.AIM To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 transcription.METHODS Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family POTE.According to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activity of the mitogen activated protein kinase and extracellular signal regulated kinase 1/2 signaling pathways,which are potentially involved in the regulation of thrombopoietin-dependent signaling and further impair proplatelet formation by megakaryocytes(MKs)[11].However,the positive regulators of ANKRD26,which might be associated with THC2 pathology,are still unknown.

The impact of chemotherapy on cognitive function of breast cancer patient

Objective:Chemotherapy significantly improved the survival of breast cancer,but also brings various symptoms and psychological distresses.Cognitive dysfunction was usually ignored.This study aimed to investigate the changes in cognitive function during chemotherapy and its influence on the quality of life in breast cancer patients.Methods:Female patients with newly diagnosed breast cancer have prospectively enrolled in this study.Participants investigated and completed questionnaires at four-time points:pre-chemotherapy(T1),post-chemotherapy(T2),6 months(T3)and 12 months(T4)after the completion of chemotherapy.The Functional Assessment of Cancer Therapy-Cognitive scale and the Functional Assessment of Cancer Therapy-Breast Cancer scale used was to assess the cognitive function and the quality of life,respectively.Data were analyzed using descriptive and repeated-measures analysis of variance statistics.Results:One hundred and eighty-three patients participated in the study and completed questionnaires at least 2 times.The mean score of cognitive function and the quality of life were significantly different at a different time point(P<0.05 for all).The trends of cognitive scores shown that the most serious damage of cognitive function appeared after beginning chemotherapy and followed by a slowly turn back after the completion of chemotherapy.The trend of the mean score of the quality of life after chemotherapy was similar to that of the cognitive score.The degree of cognitive dysfunction was significantly associated with the score of the quality of life at each time point after chemotherapy(P<0.05).Conclusion:Chemotherapy is closely associated with a cognitive impairment,which contributes to a significant decrease in the quality of life of patients with breast cancer.

The prognostic value of baseline circulating tumor cells in patients with metastatic breast cancer: a meta-analysis

Objective:The prognostic value of circulating tumor cells(CTCs)in metastatic breast cancer(MBC)patients was contentious.A meta-analysis was conducted to evaluate whether MBC patients’clinical outcomes could be predicted by CTCs detection.Methods:Relevant published studies were searched through electronic databases from January 1990 to February 2018,among which,those investigated the correlation between CTCs and clinical outcomes of progression-free survival and overall survival in MBC patients were involved.The hazard ratios(HR)and confidence intervals(CI)in the studies were extracted from the study using random or fixed effects model,and the meta-analysis was conducted.The prognostic value of tumor cells in patients with different subtypes was estimated by subgroup analysis.Results:Twenty-one eligible studies enrolling 3,837 patients were appropriate for pooled analysis.Progression-free survival(HR,1.66;95%CI,1.47–1.87;P=0.000)and overall survival(HR,2.51;95%CI,2.13–2.96;P=0.000)were worse in patients with CTCs-positive.Subtypes of hormone receptor(HorR)positive,human epidermal growth factor receptor-2(HER2)negative and triple negative with presence of CTCs showed a statistically significant worse PFS and OS.However,CTCs detection presented no prognostic value in patients with HorR-negative or HER2-positive subtypes.Conclusion:The enumeration of CTCs at baseline in patients with MBC subtypes of HorR-positive,HER2-negative and triple negative is connected with disease progression and poor survival,but inappropriate for HorR-negative and HER2-positive subtypes.