Objective： Detecting the expression and mutation of human telomeric repeat binding factor （hTRF1） in 10 malignant hematopoietic cell line cells on the base of determining its genomic structure and its four pseudoge...Objective： Detecting the expression and mutation of human telomeric repeat binding factor （hTRF1） in 10 malignant hematopoietic cell line cells on the base of determining its genomic structure and its four pseudogenes to clarify ifhTRF1 mutation is one of the factors of the activation of telomerase. Methods： hTRFlcDNA sequences were obtained from GenBank, its genome structure and pseudogenes were forecasted by BLAST and other biology information programs and then testified by sequencing. Real-time RT-PCR was used to detect the expression of h TRFlmRNA in 10 cell line cells, including myelogenous leukemia cell lines K562, HL-60, U-937, NB4, THP-I, HEL and Dami; lymphoblastic leukemia cell lines 6T-CEM, Jurkat and Raji. Telomerase activities of cells were detected by using telomeric repeat amplification （TRAP）-ELISA protocol. PCR and sequencing were used to detect mutation of each exon ofhTRF1 in 10 cell line cells. Results： hTRF1 gene, mapped to 8q13, was divided into 10 exons and spans 38.6 kb. Four processed pseudogenes ofhTRF1 located on chromosome 13, 18, 21 and X respectively, was named as ψhTRFI-13, ψhTRFI-18, ψhTRF1-21 and ψhTRFI-X respectively. All cell line cells showed positive telomerase activity. The expression of hTRF1 was significantly lower in malignant hematopoietic cell lines cells （0.0338, 0.0108-0.0749） than in normal mononuclear cells （0.0493, 0.0369-0.128） （P=0.004）. But no significant mutation was found in all exons of hTRF1 in 10 cell line cells. Four variants were found in part ofintron 1, 2 and 8 ofhTRF1. Their infection on gene function is unknown and needs further studies. Conclusion： hTRF1 mutation is probably not one of the main factors for telomerase activation in malignant hematopoietic disease.展开更多
stem cell transplantation （allo-SCT） is a potential cure for patients with malignant lymphoma that is based on the graft-versus-lymphoma （GVL） effect. Myeloablative conditioning allo-SCT is associated with high mo...stem cell transplantation （allo-SCT） is a potential cure for patients with malignant lymphoma that is based on the graft-versus-lymphoma （GVL） effect. Myeloablative conditioning allo-SCT is associated with high mortality and morbidity, particularly in patients older than 45 years, heavily pretreated patients （prior hematopoietic stem cell transplantation or more than two lines of conventional chemotherapy） or patients affected by other comorbidities. Therefore, conventional allo-SCT is restricted to younger patients （〈50 to 55 years） in good physical condition. Over the last decade, allo-SCT with reduced-intensity conditioning （RIC-allo-SCT） has been increasingly used to treat patients with lymphoma. This treatment is associated with lower toxicity and substantial decrease in the incidence of transplant- related mortality, and has the potential to lead to long-term remissions. Therefore, patients who are not suitable to undergo conventional allo-SCT can benefit from the potentially curative GVL effects of allo-SCT. Although RIC-allo-SCT has improved the survival of lymphoma patients, high post-transplant relapse rates or disease progression mainly results in treatment failure. Thus, further improvement is clearly needed. The role and timing of RIC-allo-SCT in the treatment of lymphoma remains unclear. Therefore, more prospective studies should clarify the effectiveness of this method. In this article, we review the recent literature on RIC-alIo-SCT as a treatment for major lymphoma subtypes. Areas that require further investigation in the context of clinical trials are also highlighted.展开更多
Long non-coding RNAs(lncRNAs)are defined as a class of nonprotein-coding transcripts greater than 200 nucleotides in length,which have diverse functions in development and diseases including hematopoiesis.Recent advan...Long non-coding RNAs(lncRNAs)are defined as a class of nonprotein-coding transcripts greater than 200 nucleotides in length,which have diverse functions in development and diseases including hematopoiesis.Recent advances have revealed that lncRNAs regulate hematopoietic development at almost every stage,including differentiation of the myelocyte,lymphocyte,and erythrocyte.Abnormal regulation of the lncRNAs may block aspects of blood development,which can lead to different types of hematopoietic disorders.These findings highlight the role of lncRNAs as potential therapeutic tools in malignant hematopoiesis.In this review,we summarize recent progress in the study of functional lncRNAs associated with blood development,as well as dysregulated lncRNAs involved in diverse blood diseases by interacting with crucial susceptibility genes in different pathways.In addition,we discuss genome-wide studies on lncRNAs,which are helpful for genome screening and in-depth functional study of lncRNAs associated with blood development and disease.展开更多
文摘Objective： Detecting the expression and mutation of human telomeric repeat binding factor （hTRF1） in 10 malignant hematopoietic cell line cells on the base of determining its genomic structure and its four pseudogenes to clarify ifhTRF1 mutation is one of the factors of the activation of telomerase. Methods： hTRFlcDNA sequences were obtained from GenBank, its genome structure and pseudogenes were forecasted by BLAST and other biology information programs and then testified by sequencing. Real-time RT-PCR was used to detect the expression of h TRFlmRNA in 10 cell line cells, including myelogenous leukemia cell lines K562, HL-60, U-937, NB4, THP-I, HEL and Dami; lymphoblastic leukemia cell lines 6T-CEM, Jurkat and Raji. Telomerase activities of cells were detected by using telomeric repeat amplification （TRAP）-ELISA protocol. PCR and sequencing were used to detect mutation of each exon ofhTRF1 in 10 cell line cells. Results： hTRF1 gene, mapped to 8q13, was divided into 10 exons and spans 38.6 kb. Four processed pseudogenes ofhTRF1 located on chromosome 13, 18, 21 and X respectively, was named as ψhTRFI-13, ψhTRFI-18, ψhTRF1-21 and ψhTRFI-X respectively. All cell line cells showed positive telomerase activity. The expression of hTRF1 was significantly lower in malignant hematopoietic cell lines cells （0.0338, 0.0108-0.0749） than in normal mononuclear cells （0.0493, 0.0369-0.128） （P=0.004）. But no significant mutation was found in all exons of hTRF1 in 10 cell line cells. Four variants were found in part ofintron 1, 2 and 8 ofhTRF1. Their infection on gene function is unknown and needs further studies. Conclusion： hTRF1 mutation is probably not one of the main factors for telomerase activation in malignant hematopoietic disease.
文摘stem cell transplantation （allo-SCT） is a potential cure for patients with malignant lymphoma that is based on the graft-versus-lymphoma （GVL） effect. Myeloablative conditioning allo-SCT is associated with high mortality and morbidity, particularly in patients older than 45 years, heavily pretreated patients （prior hematopoietic stem cell transplantation or more than two lines of conventional chemotherapy） or patients affected by other comorbidities. Therefore, conventional allo-SCT is restricted to younger patients （〈50 to 55 years） in good physical condition. Over the last decade, allo-SCT with reduced-intensity conditioning （RIC-allo-SCT） has been increasingly used to treat patients with lymphoma. This treatment is associated with lower toxicity and substantial decrease in the incidence of transplant- related mortality, and has the potential to lead to long-term remissions. Therefore, patients who are not suitable to undergo conventional allo-SCT can benefit from the potentially curative GVL effects of allo-SCT. Although RIC-allo-SCT has improved the survival of lymphoma patients, high post-transplant relapse rates or disease progression mainly results in treatment failure. Thus, further improvement is clearly needed. The role and timing of RIC-allo-SCT in the treatment of lymphoma remains unclear. Therefore, more prospective studies should clarify the effectiveness of this method. In this article, we review the recent literature on RIC-alIo-SCT as a treatment for major lymphoma subtypes. Areas that require further investigation in the context of clinical trials are also highlighted.
基金supported by the National Basic Research Program of China(2011CB8113015,2011CBA0110)National Natural Science Foundation of China(81270629)
文摘Long non-coding RNAs(lncRNAs)are defined as a class of nonprotein-coding transcripts greater than 200 nucleotides in length,which have diverse functions in development and diseases including hematopoiesis.Recent advances have revealed that lncRNAs regulate hematopoietic development at almost every stage,including differentiation of the myelocyte,lymphocyte,and erythrocyte.Abnormal regulation of the lncRNAs may block aspects of blood development,which can lead to different types of hematopoietic disorders.These findings highlight the role of lncRNAs as potential therapeutic tools in malignant hematopoiesis.In this review,we summarize recent progress in the study of functional lncRNAs associated with blood development,as well as dysregulated lncRNAs involved in diverse blood diseases by interacting with crucial susceptibility genes in different pathways.In addition,we discuss genome-wide studies on lncRNAs,which are helpful for genome screening and in-depth functional study of lncRNAs associated with blood development and disease.
