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A prognostic indicator in some acute myeloid leukemia patients
The following algorithms are available in Special Instructions:
-Acute Myeloid Leukemia: Testing Algorithm
-Acute Myeloid Leukemia: Relapsed with Previous Remission Testing Algorithm
The FMS-like tyrosine gene (FLT3) codes for a transmembrane receptor/signaling protein (FLT3) of the tyrosine kinase group. Binding of FLT3 ligand to the FLT3 receptor ultimately leads to production of proteins that cause cell growth and inhibit cell death through apoptosis. Recently, mutations in FLT3 have been found in some hematopoietic neoplasms, and are particularly common in adult acute myeloid leukemia (AML) with an overall incidence of approximately 20% to 30%. The highest mutation rates are seen in adult patients with AML and normal- or intermediate-risk cytogenetics, and patients with acute promyelocytic leukemia.
The most common FLT3 mutation consists of internal tandem duplication (ITD) of DNA sequences found in exons 14 or 15. In some subgroups of adults with AML, the presence of an FLT3 ITD mutation has been found to be an adverse prognostic indicator. The second most common mutation is a point mutation in the codon for an aspartate residue (D835) that resides in the activation loop of the FLT3 protein. D835 mutations have been identified in approximately 7% of AML cases but, at this time, it is not clear if the presence of this mutation has any prognostic significance. It is thought that both types of FLT3 mutations lead to constitutive (always present, independent of internal or external stimuli) FLT3 activation.
Identification of an FLT3 mutation in AML is clinically useful not only because of the prognostic information it provides, but also because FLT3-inhibitory drugs have shown promise as useful therapeutic agents.
An interpretive report will be provided.
An interpretive report will be issued indicating whether the FLT3 internal tandem duplication or D835 mutation, or both, were detected.
Mutation status will be indicated as positive or negative. If internal tandem duplication (ITD) positive, an allelic ratio will be reported.
This test is not designed for monitoring residual disease following treatment and the following should be noted: the sensitivity of the test is less than other methods designed for residual disease testing and there have been several reports of FLT3 mutations being lost or gained in neoplastic cells following treatment.
1. Levis M, Small D: FLT3: ITDoes matter in leukemia. Leukemia 2003 September;17:1738-1752
2. Gilliland DG, Griffin JD: The roles of FLT3 in hematopoiesis and leukemia. Blood 2002 September 1;100(5):1532-1542