Technical Notes
Quest PDGFRa
(FIP1L1-PDGFRa Mutation for Hypereosinophilic syndrome HES, Chronic eosinophilic leukemia (CEL)
Systemic Mast Cell Disorder-eos (SMCD-eos))
Oncogenic fusion gene Fip1-like1 (FIP1L1--PDGFRa) is formed as a result of an interstitial deletion of small chromosome fragment (approximately 800 bp) involving chromosome 4q12. The FIP1L1-PDGFR fusion protein transforms hematopoietic cells. The presence of this mutation has been identified as a cause of:
- Hypereosinophilic syndrome HES
- F/P-positive chronic eosinophilic leukemia (CEL)
- Systemic Mast Cell Disorder-eos (SMCD-eos)
The kinase activity of transformed haematopoietic cells is inhibited by imatinib at, cellular 50% inhibitory concentration (IC50) 100-fold lower than BCR-ABL.
Patients with FIP1L1-PDGFRa-positive eosinophilic disorders are likely to obtain clinical, hematologic, and even molecular remissions with standard-dose (400 mg/d) OR low dose (100 mg/d) imatinib therapy.
Presence of fusion gene stratifies patients for treatment with low dosage of imatinib
Methodology:
Patients DNA would be isolated, purified and subjected to PCR amplification using primers & Taqman probes. An
additional amplification directed at GAPDH would be performed as a control for sample DNA quality.