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Dietary L-leucine improves the anemia in a mouse model for Diamond-Blackfan anemia.

Jaako, Pekka LU ; Debnath, Shubhranshu LU ; Olsson, Karin LU ; Bryder, David LU ; Flygare, Johan LU and Karlsson, Stefan LU (2012) In Blood 120(11). p.2225-2228
Abstract
Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes encoding for ribosomal proteins. Recently, a case study reported a patient who became transfusion-independent in response to treatment with the amino acid L-leucine. Therefore, we have validated the therapeutic effect of L-leucine using our recently generated mouse model for RPS19-deficient DBA. Administration of L-leucine significantly improved the anemia in Rps19-deficient mice (19 % improvement in hemoglobin concentration; 18% increase in the number of erythrocytes), increased the bone marrow cellularity and alleviated stress hematopoiesis. Furthermore, the therapeutic response to L-leucine appeared specific for... (More)
Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes encoding for ribosomal proteins. Recently, a case study reported a patient who became transfusion-independent in response to treatment with the amino acid L-leucine. Therefore, we have validated the therapeutic effect of L-leucine using our recently generated mouse model for RPS19-deficient DBA. Administration of L-leucine significantly improved the anemia in Rps19-deficient mice (19 % improvement in hemoglobin concentration; 18% increase in the number of erythrocytes), increased the bone marrow cellularity and alleviated stress hematopoiesis. Furthermore, the therapeutic response to L-leucine appeared specific for Rps19-deficient hematopoiesis and was associated with downregulation of p53 activity. Our study supports the rationale for clinical trials of L-leucine as a therapeutic agent for DBA. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
120
issue
11
pages
2225 - 2228
publisher
American Society of Hematology
external identifiers
  • wos:000309044200014
  • pmid:22791294
  • scopus:84866314916
ISSN
1528-0020
DOI
10.1182/blood-2012-05-431437
language
English
LU publication?
yes
id
358bfd23-4e01-461f-b0f9-4d3d0060a7fe (old id 2967180)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22791294?dopt=Abstract
date added to LUP
2012-08-09 18:40:49
date last changed
2017-11-19 04:16:24
@article{358bfd23-4e01-461f-b0f9-4d3d0060a7fe,
  abstract     = {Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes encoding for ribosomal proteins. Recently, a case study reported a patient who became transfusion-independent in response to treatment with the amino acid L-leucine. Therefore, we have validated the therapeutic effect of L-leucine using our recently generated mouse model for RPS19-deficient DBA. Administration of L-leucine significantly improved the anemia in Rps19-deficient mice (19 % improvement in hemoglobin concentration; 18% increase in the number of erythrocytes), increased the bone marrow cellularity and alleviated stress hematopoiesis. Furthermore, the therapeutic response to L-leucine appeared specific for Rps19-deficient hematopoiesis and was associated with downregulation of p53 activity. Our study supports the rationale for clinical trials of L-leucine as a therapeutic agent for DBA.},
  author       = {Jaako, Pekka and Debnath, Shubhranshu and Olsson, Karin and Bryder, David and Flygare, Johan and Karlsson, Stefan},
  issn         = {1528-0020},
  language     = {eng},
  number       = {11},
  pages        = {2225--2228},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Dietary L-leucine improves the anemia in a mouse model for Diamond-Blackfan anemia.},
  url          = {http://dx.doi.org/10.1182/blood-2012-05-431437},
  volume       = {120},
  year         = {2012},
}