As a peptide hormone, CLV3 restricts the stem cell number in shoot apical meristem （SAM） by interacting with CLV1/CLV2/CRN/RPK2 receptor complexes. To elucidate how the function of the CLV3 peptide in SAM maintenanc...As a peptide hormone, CLV3 restricts the stem cell number in shoot apical meristem （SAM） by interacting with CLV1/CLV2/CRN/RPK2 receptor complexes. To elucidate how the function of the CLV3 peptide in SAM maintenance is established at the amino acid （AA） level, alanine substitutions were performed by introducing point mutations to individual residues in the peptide-coding region of CLV3 and its flanking sequences. Constructs carrying such substitutions, expressed under the control of CLV3 regulatory elements, were transformed to the clv3-2 null mutant to evaluate their efficiencies in complementing its defects in SAMs in vivo. These studies showed that aspartate-8, histidine-11, glycine-6, proline-4, arginine-1, and proline-9, arranged in an order of importance, were critical, while threonine-2, valine-3, serine-5, and the previously assigned hydroxylation and arabinosylation residue proline-7 were trivial for the endogenous CLV3 function in SAM maintenance. In contrast, substitutions of flanking residues did not impose much damage on CLV3. Complementation of different alanine-substituted constructs was confirmed by measurements of the sizes of SAMs and the WUS expression levels in transgenic plants. These studies established a complete contribution map of individual residues in the peptide-coding region of CLV3 for its function in SAM, which may help to understand peptide hormones in general.展开更多
BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research...BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.展开更多
Plant stem cells are a small group of cells with a self-renewal capacity and serve as a steady supply of precursor cells to form new differentiated tissues and organs in plants.Root stem cells and shoot stem cells,whi...Plant stem cells are a small group of cells with a self-renewal capacity and serve as a steady supply of precursor cells to form new differentiated tissues and organs in plants.Root stem cells and shoot stem cells,which are located in the root apical meristem and in the shoot apical meristem,respectively,play a critical role in plant longitudinal growth.These stem cells in shoot and root apical meristems remain as pluripotent state throughout the lifespan of the plant and control the growth and development of plants.The molecular mechanisms of initiation and maintenance of plant stem cells have been extensively investigated.In this review,we mainly discuss how the plant phytohormones,such as auxin and cytokinin,coordinate with the key transcription factors to regulate plant stem cell initiation and maintenance in root and shoot apical meristems.In addition,we highlight the common regulatory mechanisms of both root and shoot apical meristems.展开更多
Recently, the prognosis of multiple myeloma has been improved by using high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT), bortezomib, and immunomodulatory drugs including ...Recently, the prognosis of multiple myeloma has been improved by using high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT), bortezomib, and immunomodulatory drugs including thalidomide and lenalidomide. On the other hand, treatment strategy remains difficult for refractory and relapse cases. Here, we report the successful treatment of low-dose lenalidomide maintenance therapy followed by salvage ASCT in a heavily treated patient with multiple myeloma. This 58-year-old woman with IgG-λ multiple myeloma had a 5th recurrence in June, 2011. It was 7 years post-diagnosis, and she had received conventional therapies such as VAD, MP therapy. Furthermore, the patient had already been treated with ASCT, bortezomib, and thalidomide therapy. At the 5th recurrence, she had extramedullary plasmacytoma in the left orbit. She initially received bortezomib and dexamethasone therapy as induction therapy. After peripheral blood stem cell collection, radiation therapy was performed. The patient then received a second ASCT. Three months later, the response was very good partial response. Finally, the patient was treated with 5 mg/day lenalidomide orally as a maintenance therapy, and she achieved stringent complete response after 2 months according to International Myeloma Working Group response criteria. Low-dose lenalidomide maintenance therapy might be also useful for ASCT as salvage therapy, although further studies are warranted.展开更多
Human acute myeloid leukemia(AML)is a fatal hematologic malignancy characterized with accumulation of myeloid blasts and differentiation arrest.The development of AML is associated with a serial of genetic and epigene...Human acute myeloid leukemia(AML)is a fatal hematologic malignancy characterized with accumulation of myeloid blasts and differentiation arrest.The development of AML is associated with a serial of genetic and epigenetic alterations mainly occurred in hematopoietic stem and progenitor cells(HSPCs),which change HSPC state at the molecular and cellular levels and transform them into leukemia stem cells(LSCs).LSCs play critical roles in leukemia initiation,progression,and relapse,and need to be eradicated to achieve a cure in clinic.Key to successfully targeting LSCs is to fully understand the unique cellular and molecular mechanisms for maintaining their stemness.Here,we discuss LSCs in AML with a focus on identification of unique biological features of these stem cells to decipher the molecular mechanisms of LSC maintenance.展开更多
基金This work was supported by the Ministry of China （2007CB948200）, Chinese of Science and Technology Academy of Sciences （1105000003 and 200904910192008）, and the National Natural Science Foundation of China （30821007 and 31000623）. ACKNOWLEDGMENTS We thank Dr Trevor L. Wang at the John Innes Centre, UK, for critical reading of the manuscript Prof. Kexue Xu at the Institute of Botany, Chinese Academy of Sciences, for suggestions regarding the statistica~ data analysis and Dr Wei Gao at Beijing Forestry University for discussions of the results. No conflict of interest declared.
文摘As a peptide hormone, CLV3 restricts the stem cell number in shoot apical meristem （SAM） by interacting with CLV1/CLV2/CRN/RPK2 receptor complexes. To elucidate how the function of the CLV3 peptide in SAM maintenance is established at the amino acid （AA） level, alanine substitutions were performed by introducing point mutations to individual residues in the peptide-coding region of CLV3 and its flanking sequences. Constructs carrying such substitutions, expressed under the control of CLV3 regulatory elements, were transformed to the clv3-2 null mutant to evaluate their efficiencies in complementing its defects in SAMs in vivo. These studies showed that aspartate-8, histidine-11, glycine-6, proline-4, arginine-1, and proline-9, arranged in an order of importance, were critical, while threonine-2, valine-3, serine-5, and the previously assigned hydroxylation and arabinosylation residue proline-7 were trivial for the endogenous CLV3 function in SAM maintenance. In contrast, substitutions of flanking residues did not impose much damage on CLV3. Complementation of different alanine-substituted constructs was confirmed by measurements of the sizes of SAMs and the WUS expression levels in transgenic plants. These studies established a complete contribution map of individual residues in the peptide-coding region of CLV3 for its function in SAM, which may help to understand peptide hormones in general.
文摘BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.
基金This work is supported by the Shandong Province Natural Science Foundation of Major Basic Research Program(2017C03)by Qingdao’s Leading Technology Innovator Project,and by Youth Interdisciplinary Science and Innovative Research Groups of Shandong University(Grant No.2020QNQT014).
文摘Plant stem cells are a small group of cells with a self-renewal capacity and serve as a steady supply of precursor cells to form new differentiated tissues and organs in plants.Root stem cells and shoot stem cells,which are located in the root apical meristem and in the shoot apical meristem,respectively,play a critical role in plant longitudinal growth.These stem cells in shoot and root apical meristems remain as pluripotent state throughout the lifespan of the plant and control the growth and development of plants.The molecular mechanisms of initiation and maintenance of plant stem cells have been extensively investigated.In this review,we mainly discuss how the plant phytohormones,such as auxin and cytokinin,coordinate with the key transcription factors to regulate plant stem cell initiation and maintenance in root and shoot apical meristems.In addition,we highlight the common regulatory mechanisms of both root and shoot apical meristems.
文摘Recently, the prognosis of multiple myeloma has been improved by using high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT), bortezomib, and immunomodulatory drugs including thalidomide and lenalidomide. On the other hand, treatment strategy remains difficult for refractory and relapse cases. Here, we report the successful treatment of low-dose lenalidomide maintenance therapy followed by salvage ASCT in a heavily treated patient with multiple myeloma. This 58-year-old woman with IgG-λ multiple myeloma had a 5th recurrence in June, 2011. It was 7 years post-diagnosis, and she had received conventional therapies such as VAD, MP therapy. Furthermore, the patient had already been treated with ASCT, bortezomib, and thalidomide therapy. At the 5th recurrence, she had extramedullary plasmacytoma in the left orbit. She initially received bortezomib and dexamethasone therapy as induction therapy. After peripheral blood stem cell collection, radiation therapy was performed. The patient then received a second ASCT. Three months later, the response was very good partial response. Finally, the patient was treated with 5 mg/day lenalidomide orally as a maintenance therapy, and she achieved stringent complete response after 2 months according to International Myeloma Working Group response criteria. Low-dose lenalidomide maintenance therapy might be also useful for ASCT as salvage therapy, although further studies are warranted.
基金The National Key Research and Development Program of China(2017YFA0505600)The National Natural Science Foundation of China(81722003,81870124)+1 种基金The Wuhan Science and Technology Program for Application and Basic Research Project(2018060401011325)The Hubei Provincial Natural Science Foundation for Creative Research Group(2018CFA018).
文摘Human acute myeloid leukemia(AML)is a fatal hematologic malignancy characterized with accumulation of myeloid blasts and differentiation arrest.The development of AML is associated with a serial of genetic and epigenetic alterations mainly occurred in hematopoietic stem and progenitor cells(HSPCs),which change HSPC state at the molecular and cellular levels and transform them into leukemia stem cells(LSCs).LSCs play critical roles in leukemia initiation,progression,and relapse,and need to be eradicated to achieve a cure in clinic.Key to successfully targeting LSCs is to fully understand the unique cellular and molecular mechanisms for maintaining their stemness.Here,we discuss LSCs in AML with a focus on identification of unique biological features of these stem cells to decipher the molecular mechanisms of LSC maintenance.
