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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2006-12-27
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pubmed:abstractText |
Point mutations in the gene for the granulocyte colony-stimulating factor (G-CSF) receptor CSF3R have been implicated in the progression of severe congenital neutropenia (CN) to leukemia. In this study we present data on a total of 218 patients with chronic neutropenia, including 148 patients with CN (23/148 with secondary malignancies). We detected CSF3R nonsense mutations at 17 different nucleotide positions (thereof 10 new mutations) which lead to a loss of 1 to all 4 tyrosine residues in the intracellular domain of the receptor. Of 23 patients with CN with signs of malignant transformation, 18 (78%) were shown to harbor a CSF3R mutation, indicating that these mutations, although not a necessary condition, are highly predictive for malignant transformation even if detected in a low percentage of transcripts. In serial analyses of 50 patients with CSF3R mutations we were able to follow the clonal dynamics of mutated cells. We could demonstrate that even a highly clonal hematopoiesis did not inevitably show a rapid progression to leukemia. Our results strongly suggest that acquisition of a CSF3R mutation is an early event in leukemogenesis that has to be accompanied by cooperating molecular events, which remain to be defined.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
109
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
93-9
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pubmed:meshHeading |
pubmed-meshheading:16985178-Adolescent,
pubmed-meshheading:16985178-Adult,
pubmed-meshheading:16985178-Age of Onset,
pubmed-meshheading:16985178-Anemia, Aplastic,
pubmed-meshheading:16985178-Case Management,
pubmed-meshheading:16985178-Cell Transformation, Neoplastic,
pubmed-meshheading:16985178-Child,
pubmed-meshheading:16985178-Child, Preschool,
pubmed-meshheading:16985178-Chronic Disease,
pubmed-meshheading:16985178-Clone Cells,
pubmed-meshheading:16985178-Codon, Nonsense,
pubmed-meshheading:16985178-DNA Mutational Analysis,
pubmed-meshheading:16985178-Disease Progression,
pubmed-meshheading:16985178-Disease Susceptibility,
pubmed-meshheading:16985178-Female,
pubmed-meshheading:16985178-Granulocyte Colony-Stimulating Factor,
pubmed-meshheading:16985178-Hematopoiesis,
pubmed-meshheading:16985178-Humans,
pubmed-meshheading:16985178-Leukemia,
pubmed-meshheading:16985178-Male,
pubmed-meshheading:16985178-Middle Aged,
pubmed-meshheading:16985178-Mutagenesis,
pubmed-meshheading:16985178-Mutation,
pubmed-meshheading:16985178-Myelodysplastic Syndromes,
pubmed-meshheading:16985178-Neutropenia,
pubmed-meshheading:16985178-Protein Structure, Tertiary,
pubmed-meshheading:16985178-RNA, Messenger,
pubmed-meshheading:16985178-Receptors, Colony-Stimulating Factor
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pubmed:year |
2007
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pubmed:articleTitle |
Incidence of CSF3R mutations in severe congenital neutropenia and relevance for leukemogenesis: Results of a long-term survey.
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pubmed:affiliation |
Department of Pediatric Hematology and Oncology, Hannover Medical School, Germany. germeshausen.manuela@mh-hannover.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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