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FLT3ITD

Background

The FLT3 gene encodes a tyrosine kinase receptor that regulates proliferation and differentiation of hematopoietic stem cells.   An internal tandem duplication (ITD) of varying size and placement within exons 14 and 15 is thought to cause a conformational change in the juxtamembrane domain of the FLT3 receptor leading to ligand independent receptor dimerization and thus unregulated receptor kinase activity.

Clinical Significance

An internal tandem duplication within exons 14 and 15 has been found to be an independent prognostic factor for poor outcome in both pediatric (3) and adult (4) acute myeloid leukemia (AML) patients.  Prognostic significance of FLT3/ITD may be modified by the allelic ratio of the FLT3-ITD (1, 2).

Method

DNA is extracted from peripheral blood or bone marrow samples.  Polymerase chain reaction (PCR) amplifies the target sequence in exons 14 and 15 of the FLT3 gene.   Capillary electrophoresis of the PCR product reveals a molecular weight band higher than the wild-type FLT3 PCR product when an ITD is present.  Patient samples are run in duplicate with appropriate positive and negative controls. The FLT3-ITD allelic ratio is calculated as the ratio of the peak height of the mutant product to the peak height of the wild-type product.

References

1. Blood (2006);108(12):3654-3661 http://bloodjournal.hematologylibrary.org/cgi/content/abstract/108/12/3654

2. Blood (2002);99(12):4326-4335 http://bloodjournal.hematologylibrary.org/cgi/content/abstract/99/12/4326

3. Blood (2001);97(1): 89-94
http://bloodjournal.hematologylibrary.org/cgi/content/abstract/97/1/89

4. Blood (1999);93(9):3074-3080
http://bloodjournal.hematologylibrary.org/cgi/content/abstract/93/9/3074

Questions pertaining to testing may be addressed to the Molecular Oncology Laboratory at 206-667-2592