Prior research establishing that bone interacts in coordination with the bone marrow microenvironment(BMME)to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell populat...Prior research establishing that bone interacts in coordination with the bone marrow microenvironment(BMME)to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell populations.Recent advances in intravital imaging has suggested that the expansion of hematopoietic stem cells(HSCs)and acute myeloid leukemia cells is restricted to bone marrow microdomains during a distinct stage of bone remodeling.These findings indicate that dynamic bone remodeling likely imposes additional heterogeneity within the BMME to yield differential clonal responses.A holistic understanding of the role of bone remodeling in regulating the stem cell niche and how these interactions are altered in age-related hematological malignancies will be critical to the development of novel interventions.To advance this understanding,herein,we provide a synopsis of the cellular and molecular constituents that participate in bone turnover and their known connections to the hematopoietic compartment.Specifically,we elaborate on the coupling between bone remodeling and the BMME in homeostasis and age-related hematological malignancies and after treatment with bone-targeting approaches.We then discuss unresolved questions and ambiguities that remain in the field.展开更多
Total body irradiation (TBI) is conditioning regimen in children with acute lymphoblastic leukemia (ALL) with a very high risk of relapse or in those who have not achieved remission and have relapsed and subsequently ...Total body irradiation (TBI) is conditioning regimen in children with acute lymphoblastic leukemia (ALL) with a very high risk of relapse or in those who have not achieved remission and have relapsed and subsequently received allogenic hematopoietic stem cell transplantation (HSCT). A retrospective evaluation of 33 ALL patients in full remission with an indication of HSCT was performed to evaluate overall survival (OS) and event-free survival (EFS). The inclusion criteria included a myeloablative conditioning regimen of TBI at a dose of 600 cGy. The observed OS at 5 years was 50%, and the EFS of 32% we observed difference in the EFS stem cell origin;the peripheral blood (PB) 60%, and the umbilical cord blood (UC) accounted for 40%. Overall, 45% had a documented chimerism. The OS at 5 years from patients with chimeras was 75%, while those without chimeras had an OS at 5 years of 25%. The mortality in the first 100 days was 24%. A total of 24.2% of children presented with acute graft versus-host disease (GVHD), while 33% had chronic GVHD. Currently, there is no general agreement among all international centers regarding the optimum TBI dose. Our study reports an acceptable range of adverse events with a relatively low dose of 600 cGy.展开更多
1 Introduction Cardiac amyloid(CA)is characterized by inexorably progressive heart failure making early diagnosis and treatment imperative.This article will review the pathophysiology,clinical presentation,diagnosis,p...1 Introduction Cardiac amyloid(CA)is characterized by inexorably progressive heart failure making early diagnosis and treatment imperative.This article will review the pathophysiology,clinical presentation,diagnosis,prognostication and treatment of patients with CA.2 Pathophysiology CA is the result of extracellular deposition of a misfolded protein into cardiac tissue,forming insoluble aggregations of rigid,nonbranching 10 nm wide fibrils.This causes impaired cardiac function by disrupting cardiac architecture,direct myotoxicity and ischemic injury secondary to infiltration of intramyocardial vessels.展开更多
基金supported by awards from the National Institute of Health R21AR069789&R01 AG059775(to LX),R01 AG076786&R01 AG079556The Henry and Marilyn Taub Foundation+4 种基金the Edward P.Evans Foundationthe Mangurian Foundationthe National Aeronautics and Space Administration(to LMC)NIH R21 AR081050,R01 AR056702,P30 AR069655&P50 AR072000(to EMS)University of Rochester Aging Institute and the Dresner MDS foundation(to SY)。
文摘Prior research establishing that bone interacts in coordination with the bone marrow microenvironment(BMME)to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell populations.Recent advances in intravital imaging has suggested that the expansion of hematopoietic stem cells(HSCs)and acute myeloid leukemia cells is restricted to bone marrow microdomains during a distinct stage of bone remodeling.These findings indicate that dynamic bone remodeling likely imposes additional heterogeneity within the BMME to yield differential clonal responses.A holistic understanding of the role of bone remodeling in regulating the stem cell niche and how these interactions are altered in age-related hematological malignancies will be critical to the development of novel interventions.To advance this understanding,herein,we provide a synopsis of the cellular and molecular constituents that participate in bone turnover and their known connections to the hematopoietic compartment.Specifically,we elaborate on the coupling between bone remodeling and the BMME in homeostasis and age-related hematological malignancies and after treatment with bone-targeting approaches.We then discuss unresolved questions and ambiguities that remain in the field.
文摘Total body irradiation (TBI) is conditioning regimen in children with acute lymphoblastic leukemia (ALL) with a very high risk of relapse or in those who have not achieved remission and have relapsed and subsequently received allogenic hematopoietic stem cell transplantation (HSCT). A retrospective evaluation of 33 ALL patients in full remission with an indication of HSCT was performed to evaluate overall survival (OS) and event-free survival (EFS). The inclusion criteria included a myeloablative conditioning regimen of TBI at a dose of 600 cGy. The observed OS at 5 years was 50%, and the EFS of 32% we observed difference in the EFS stem cell origin;the peripheral blood (PB) 60%, and the umbilical cord blood (UC) accounted for 40%. Overall, 45% had a documented chimerism. The OS at 5 years from patients with chimeras was 75%, while those without chimeras had an OS at 5 years of 25%. The mortality in the first 100 days was 24%. A total of 24.2% of children presented with acute graft versus-host disease (GVHD), while 33% had chronic GVHD. Currently, there is no general agreement among all international centers regarding the optimum TBI dose. Our study reports an acceptable range of adverse events with a relatively low dose of 600 cGy.
文摘1 Introduction Cardiac amyloid(CA)is characterized by inexorably progressive heart failure making early diagnosis and treatment imperative.This article will review the pathophysiology,clinical presentation,diagnosis,prognostication and treatment of patients with CA.2 Pathophysiology CA is the result of extracellular deposition of a misfolded protein into cardiac tissue,forming insoluble aggregations of rigid,nonbranching 10 nm wide fibrils.This causes impaired cardiac function by disrupting cardiac architecture,direct myotoxicity and ischemic injury secondary to infiltration of intramyocardial vessels.
