FLT3 is a member of the platelet-derived growth factor receptor subfamily, with 2 types of mutations having prognostic significance in AML. FLT3 Internal Tandem Duplications (ITD) result in an in-frame duplication of a region of the juxtamembrane domain, allowing ligand-independent dimerisation of the receptor to occur, leading to activation of the kinase and the downstream signalling pathways. The second type of mutation seen in FLT3 is a point mutation in the tyrosine kinase domain (TKD) leading to a D835V amino acid substitution, again leading to ligand-independent dimerisation of the receptor and therefore activation of the kinase and the downstream signalling pathways.
In this programme, participants are provided with lyophilised cell-lines or patient derived material for FLT3 mutation status analysis. Participants are asked to submit a qualitative result as well as the size of the ITD if applicable, together with details of the methodology. Unfortunately, due to the lack of an available cell line, and the questionable clinical validity of the FLT3 D835, our FLT3 EQA programme does not cover this mutation and covers the ITD only.
Instructions for storage, reconstitution and use of the lyophilised samples are included with the samples. Three send-outs are issued per annum, with each send-out consisting of two samples. Periodically, additional educational samples may be dispatched alongside scored trial samples. FLT3 mutations, if present, should be expected at 'diagnostic' levels.
Pre issue testing of samples for this programme is subcontracted, although the final decision about sample suitability lies with the EQA provider; no other activities in relation to this EQA programme are subcontracted.