Document Detail


Comparative analysis of MLL partial tandem duplication and FLT3 internal tandem duplication mutations in 956 adult patients with acute myeloid leukemia.
MedLine Citation:
PMID:  12759922     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Partial tandem duplication (PTD) of the MLL gene and internal tandem duplication (ITD) of the juxtamembrane region of the FLT3 receptor tyrosine kinase gene have been described in acute myeloid leukemia (AML) patients, preferentially in those with normal cytogenetics. These alterations have been associated with a poor prognosis. In our study, we analyzed the prevalence and the potential prognostic impact of these aberrations in a large unselected and well-defined cohort of 956 patients with AML. Results were correlated with cytogenetic data and clinical outcome. MLL PTD was detected by RT-PCR, subsequent nucleotide sequencing, and Southern blotting. The overall incidence was found to be 5.0% (48/956), whereas FLT3 ITD was detected in 19.2% (184/956). Sixteen cases were positive for both alterations. The rate of MLL PTD in FLT3 ITD positive patients was significantly higher than that in FLT3 ITD negative patients [16/184 (8.7%); 32/772 (4.1%); P = 0.025]. However, both aberrations were highly increased in patients with normal karyotype (MLL PTD 35/431, P = 0.004; FLT3 ITD 132/334, P < 0.001). When restricted to this subgroup, the rate of MLL PTD in patients with FLT3 mutations was not significantly increased. No statistically significant differences were detected between patients positive for MLL PTD and patients negative for MLL PTD in the rate of complete remissions or the overall survival, although we did see a significantly shorter disease-free survival in patients age 60 or younger. In conclusion, although there is an overlap in the mutational spectrum in AML with FLT3 ITD and MLL PTD mutations, our data do not support a common mechanistic basis. Although associated with inferior disease-free survival, the results of this study do not unequivocally support the notion that MLL PTD mutations represent an independent prognostic factor.
Authors:
Christine Steudel; Martin Wermke; Markus Schaich; Ulrike Schäkel; Thomas Illmer; Gerhard Ehninger; Christian Thiede
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes, chromosomes & cancer     Volume:  37     ISSN:  1045-2257     ISO Abbreviation:  Genes Chromosomes Cancer     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-05-21     Completed Date:  2003-07-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9007329     Medline TA:  Genes Chromosomes Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  237-51     Citation Subset:  IM    
Copyright Information:
Copyright 2003 Wiley-Liss, Inc.
Affiliation:
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Custav Carus der Technischen Universität Dresden, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Anemia, Refractory, with Excess of Blasts / drug therapy,  epidemiology,  genetics,  therapy
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Cohort Studies
Cytogenetic Analysis / methods
DNA-Binding Proteins / genetics*
Female
Gene Duplication*
Humans
Incidence
Leukemia, Myeloid, Acute / drug therapy,  epidemiology,  genetics*,  therapy
Male
Middle Aged
Mutation*
Myeloid-Lymphoid Leukemia Protein
Proto-Oncogene Proteins / genetics*
Proto-Oncogenes*
Receptor Protein-Tyrosine Kinases / genetics*
Tandem Repeat Sequences / genetics*
Transcription Factors*
fms-Like Tyrosine Kinase 3
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/MLL protein, human; 0/Proto-Oncogene Proteins; 0/Transcription Factors; 149025-06-9/Myeloid-Lymphoid Leukemia Protein; EC 2.7.10.1/FLT3 protein, human; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases; EC 2.7.10.1/fms-Like Tyrosine Kinase 3

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