Role of HLA match on results of hematopoietic stem cell transplantations from unrelated donors in children with acute leukemia and bone marrow failure syndromes

2017 ◽  
Vol 48 (1) ◽  
pp. 48-53 ◽  
Author(s):  
Jan Styczyński ◽  
Robert Dębski ◽  
Anna Krenska ◽  
Krzysztof Czyżewski ◽  
Natalia Bartoszewicz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Acute Leukemia ◽  
Hematopoietic Stem Cell ◽  
Bone Marrow Failure ◽  
Hematopoietic Stem ◽  
Bone Marrow Failure Syndromes ◽  
Unrelated Donors

scholarly journals RECENT ADVANCES IN HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR INHERITED BONE MARROW FAILURE SYNDROMES

JBMTCT ◽  
2020 ◽  
Vol 2 (1) ◽  
pp. 69-76
Author(s):  
Luiz Guilherme Darrigo Junior ◽  
Carmem Bomfim
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Bone Marrow Failure ◽  
Hematopoietic Stem ◽  
Bone Marrow Failure Syndromes ◽  
Risk Of Cancer

The inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders characterized by the inadequate production of at least one of the hematopoietic lineages, leading to the development of both isolated cytopenia (anemia, neutropenia, or thrombocytopenia) or pancytopenia. Different biological mechanisms justify the pathophysiological changes found in the IBMFS, emphasizing the repair pathways in Fanconi anemia (FA), maintenance of telomeres in congenital dyskeratosis, and ribosome biogenesis in Shwachman Diamond syndrome (SSD) and Blackfan Diamond anemia. These disorders are generally associated with the presence of congenital malformations and an increased risk of cancer, mainly hematological, gynecological, and head and neck neoplasms. Although the diagnosis occurs typically in childhood, adult patients, mostly below 40 years of age with signs and symptoms suggestive of IBMFS, should be investigated. Currently, hematopoietic stem cell transplantation (HSCT) is the only curative option for hematological complications related to IBMFS.  It is essential to highlight that these patients must be monitored throughout their lives to prevent or detect early treatable neoplasia.

The Zebrafish Provides Mechanistic Insights into the Role of Poly(A)-Specific Ribonuclease (PARN) in Hematopoietic Stem Cell (HSC) Homeostasis and Bone Marrow Failure

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 668-668
Author(s):  
Adam P Deveau ◽  
Andrew J Coombs ◽  
Santhosh Dhanraj ◽  
Gretchen Wagner ◽  
Yigal Dror ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Conflicts Of Interest ◽  
Bone Marrow Failure ◽  
Hematopoietic Stem ◽  
Phosphohistone H3 ◽  
Biallelic Mutations ◽  
Insight Into

Abstract Development of tissues during embryogenesis and their homeostasis after formation are highly regulated by expression of coding and non-coding RNAs. Deadenylation is a core mechanism that regulates RNA function and fate by controlling turnover, abundance and maturation of RNA. Factors that promote or inhibit deadenylation control hematopoietic stem cell (HSC) homeostasis, and inhibition of deadenylation limits differentiation of the HSCs. Importantly, RNA biogenesis has emerged as a mechanism underlying several inherited bone marrow failure syndromes (IBMFSs), such as Diamond Blackfan anemia, dyskeratosis congenita (DC) and Shwachman-Diamond syndrome. Poly(A)-specific ribonuclease (PARN) is a major deadenylation factor and demonstrates high specificity for single-stranded poly (A) tails of various RNA species. We recently identified biallelic mutations in PARN as a cause of hematopoietic failure and profound hypomyelination, similar to the severe form of DC, Hoyeraal-Hreidersson syndrome. We developed a zebrafish model to characterize the hematopoietic phenotype of a patient identified to have severe inherited bone marrow failure resulting from a combined deletion of PARN on one allele and missense mutation in the other. Zebrafish posses a single parn ortholog. Zebrafish parn protein shares homology and high sequence identity (~64%) to its human counterpart. Embryos were injected with either translation start-site or splice-site-blocking morpholino at the one-cell stage. Both morpholino injections resulted in anemic embryos at 48 hours post fertilization (hpf), as evidenced by reduced o-dianisidine staining and gata1 expression by whole-mount in situ hybrization and GFP+ red cell numbers by fluorescence-activated cell sorting (FACS). Morphant embryos also demonstrated reduced expression of myeloid cell markers including l-plastin, myeloperoxidase, and macrophage expressed gene 1 and were leukopenic as evidenced by reduced number of GFP+ myeloid cells. FACS analysis revealed that fluorescently labeled HSCs were increased in parn morphants. Early hematopoietic markers, lmo2 and fli1, expressed in hemogenic and vascular tissue respectively, were also overexpressed in parn morphants. Furthermore, there was reduced global cell proliferation in morphant embryos as determined by phosphohistone H3 antibody staining. These findings suggest that the absence of parn results in a developmental arrest at the HSC stage with an inability to differentiate into leukocyte or erythroid lineages. Similarly, human cell culture data from PARN-deficient HSC/progenitor cells demonstrated markedly reduced colony forming capacity. By modeling parn deficiency in the zebrafish, we validate for the first time an IBMFS that results from biallelic mutations in a major deadenylating protein. Moreover, our zebrafish studies provide insight into the role of parn in maintaining HSC homeostasis/differentiation as the origin of the pancytopenia observed in this patient. Permanent knockouts in the zebrafish using CRISPR/Cas9 technology are underway, which will enable tracking the hematopoietic phenotype into adulthood. These studies have set the stage for critical translational research in a rare form of bone marrow failure as well as new insight into HSC regulation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Brazilian Consensus Meeting on Pediatric Hematopoietic Stem Cell Transplantation for Acquired Aplastic Anemia and Inherited Bone Marrow Failure Syndromes

JBMTCT ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 151
Author(s):  
Luiz Guilherme Darrigo Junior ◽  
Gisele Loth ◽  
Phillip Scheinberg ◽  
Elias Hallack Atta ◽  
Carmem Bonfim
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Bone Marrow Failure ◽  
Hematopoietic Stem ◽  
Bone Marrow Failure Syndromes

THE BRAZILIAN SOCIETY FOR BLOOD AND MARROW TRANSPLANTATION (SBTMO) PRESENTS THE BRAZILIAN GUIDELINES ON HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR ACQUIRED APLASTIC ANEMIA AND INHERITED BONE MARROW FAILURE SYNDROMES

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