FLT3 D324N variant may be associated with a predisposition to different leukemia subtypes

06-05-2006

The FLT3 D324N variant may be associated with a predisposition to different subtypes of leukemia, according to a study from Germany.

"Mutations within the FLT3 gene are of growing importance for classification, risk assessment, and therapeutic targeting of acute myeloid leukemia (AML). We analyzed 656 AML patients for a recently described single-nucleotide polymorphism in the third immunoglobulin-like domain of the extracellular region of FLT3," wrote S. Schnittger and colleagues, University Hospital Grosshadern.

"The FLT3 D324N variant was present in 42 cases (6.4%), but it was not associated with a specific AML subtype and did not show an elevated leukocyte count, as do other FLT3 mutations. In remission samples, a 50% ratio of the normal to the D324N variant was detectable. Stably expressed in IL-3 [interleukin-3]-dependent Ba/F3 cells, the D324N variant did not confer receptor autophosphorylation, factor independent growth, or increased resistance to apoptotic cell death in response to varying doses of FLT3 ligand. In 400 healthy donors, the FLT3 D324N variant was detected in 6 cases (1.5%) and segregated in a family. Thus, it was shown to be a polymorphism with a lower frequency in healthy controls than in patients with AML (p <0.001). In addition, 21 of 234 CML [chronic myeloid leukemia] (9.0%) and 7 of 155 ALL [acute lymphocytic leukemia] (4.5%) cases carried the FLT3 D324N."

The researchers concluded: "Our data suggest that the FLT3 D324N variant might be associated with a predisposition to different subtypes of leukemia."

Schnittger and colleagues published the results of their research in Genes Chromosomes & Cancer (D324N single-nucleotide polymorphism in the FLT3 gene is associated with higher risk of myeloid leukemias. Genes Chromosomes Cancer, 2006;45(4):332-337).

For additional information, contact S. Schnittger, University Hospital Grosshadern, Max Lebsche Pl 31, D-81377 Munich, Germany.

The publisher of the journal Genes Chromosomes & Cancer can be contacted at: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.

Keywords: Munich, Germany, Acute Myeloid Leukemia, Immunology, Oncology, Risk Factor.

This article was prepared by Cancer Gene Therapy Week editors from staff and other reports. Copyright 2006, Cancer Gene Therapy Week via NewsRx.com.