Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the Flt3 gene View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2000-04

AUTHORS

WJC Rombouts, I Blokland, B Löwenberg, RE Ploemacher

ABSTRACT

Internal tandem duplications of the FIt3 gene (FIt3/ITDs) are present in about 18% of all AML cases and are therefore one of the most frequent somatic gene mutations in AML. Little is known about the role of FIt3/ITDs in leukemogenesis or their clinical relevance. In this study we compared 18 samples with FIt3/ITDs and 63 AML samples without these mutations with respect to clinical prognosis, cytokine responsiveness, progenitor cell content and repopulation in the NOD/SCID mouse. We found that in patients with a mutation CR rates are reduced (P=0.03) and relapse rates are increased (P=0.01), indicating the prognostic importance of FIt3/ITDs. This is also emphasized by the finding that in patients under the age of 60 years, as well as in older patients the event-free survival was more unfavorable for the mutant patients (P=0.003 and P=0.03, respectively). At diagnosis FIt3/ITD and non-mutant AML bone marrow samples did not differ in their progenitor/stem cell frequencies. Cobblestone area forming cell (CAFC) subsets showed a similar frequency distribution in mutant and non-mutant samples. In 7-day liquid cultures, FIt3/ITD samples showed a reduced growth in response to a variety of myeloid growth factors. In contrast, FIt3/ITD samples displayed a higher ability to engraft the NOD/SCID bone marrow with leukemic cells. Together these data show that the FIt3/ITD represents an important diagnostic marker for patient prognosis, and that the presence of these mutations is associated with altered proliferative ability of progenitors in vivo and in vitro. More... »

PAGES

2401731

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/sj.leu.2401731

    DOI

    http://dx.doi.org/10.1038/sj.leu.2401731

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1052319870

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/10764154


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