Better detection of FLT3 internal tandem duplication using peripheral blood plasma DNA View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2003-01

AUTHORS

I Jilani, E Estey, T Manshuri, M Caligiuri, M Keating, F Giles, D Thomas, H Kantarjian, M Albitar

ABSTRACT

Somatic mutation of the FLT3 gene as an internal tandem duplication (ITD) of the juxtamembrane domain-coding sequence causes constitutive tyrosine phosphorylation and activation. Tumor-specific DNA has been documented in the sera of patients with solid tumors even when it is in an early stage. We compared the detection of FLT3 ITD in DNA extracted from cells of bone marrow (BM) aspirations with DNA extracted from peripheral blood (PB) plasma in patients newly diagnosed with acute myeloid leukemia (AML; 85 patients), myelodysplastic syndrome (MDS; 16 patients), and acute lymphocytic leukemia (ALL; 16 patients). FLT3 ITD was detected in 18 (21%) AML samples and in one (6%) MDS sample in both cellular and plasma DNA but in none of the ALL samples. Hemizygous/homozygous FLT3 ITD was detected in five (28%) of the FLT3 ITD-positive AML using plasma DNA, whereas only four of these cases showed hemizygous/homozygous FLT3 ITD using cellular DNA. The presence of FLT3 ITD was associated with significantly shorter survival (P = 0.02) when only patients younger than 50 years of age (48 AML+MDS patients) were considered. This finding was independent of cytogenetics in this age group. However, patients with the FLT3 ITD hemizygous/homozygous phenotype had even shorter survival (P = <0.001). As expected, the presence of FLT3 ITD correlated with higher white blood cell (WBC) counts. These data demonstrate that plasma DNA is a reliable alternative resource for detecting FLT3ITD, especially the hemizygous/homozygous genotype. Furthermore, the data derived from this study support the notion that the presence of FLT3 ITD in conjunction with the absence of the wild-type FLT3 allele predicts an especially poor prognosis for patients with AML. More... »

PAGES

2402743

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.leu.2402743

DOI

http://dx.doi.org/10.1038/sj.leu.2402743

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1030985828

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12529667


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