Annotation Detail

Information
Associated Genes
PDGFRA
Associated Variants
PDGFRA BCR-PDGFRA
Associated Disease
B-cell acute lymphoblastic leukemia
Source Database
CIViC Evidence
Description
A 47-year-old man was diagnosed with pre-B-cell acute lymphoblastic leukemia. FISH and nested PCR revealed the patient had a t(4;22)(q12;11) translocation that created an in-frame BCR-PDGFRA fusion. The constitutively activating coiled-coil domain and serine/threonine kinase encoded by BCR exon 1 fused with exon 13 of PDGFRA, which retained both tyrosine kinase domains. During initial therapy, intensification, and consolidation, hyperleukocytosis persisted. Based on the presence of the BCR-PDGFRA fusion, single agent imatinib (Glivec) was administered. A complete hematological response was observed within 6 weeks as the presence of t(4;22) in the bone marrow went from a 70% down to 15%. However, the patient had a relapse in the central nervous system. Continued treatment with imatinib along with intrathecal chemotherapy achieved a meningeal remission after 2 weeks. According to the authors, this patient’s response implicates PDGFRA as a clinically actionable imatinib target.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/7990
Gene URL
https://civic.genome.wustl.edu/links/genes/38
Variant URL
https://civic.genome.wustl.edu/links/variants/2971
Rating
3
Evidence Type
Predictive
Disease
B-cell Acute Lymphoblastic Leukemia
Evidence Direction
Supports
Drug
Imatinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
12944919
Drugs
Drug NameSensitivitySupported
ImatinibSensitivitytrue