FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia.
A novel oncogenic mutation (FIP1L1-PDGFRA), which results in a constitutively activated platelet-derived growth factor receptor-alpha (PDGFRA), has been invariably associated with a primary eosinophilic disorder. The current study examines both the prevalence and the associated clinicopathologic features of this mutation in a cohort of 89 adult patients presenting with an absolute eosinophil count (AEC) of higher than 1.5 x 10(9)/L. A fluorescence in situ hybridization (FISH)-based strategy was used to detect FIP1L1-PDGFRA in bone marrow cells. None of 8 patients with reactive eosinophilia displayed the abnormality, whereas the incidence of FIP1L1-PDGFRA in the remaining 81 patients with primary eosinophilia was 14% (11 patients). None (0%) of 57 patients with the hypereosinophilic syndrome (HES) but 10 (56%) of 19 patients with systemic mast cell disease associated with eosinophilia (SMCD-eos) carried the specific mutation. The bone marrow mast cell infiltration pattern in FIP1L1-PDGFRA(+) SMCD-eos was distinctly diffuse with loose tumoral aggregates. Treatment with low-dose imatinib (100 mg/d) produced complete and durable responses in all 8 FIP1L1-PDGFRA(+) cases treated. In contrast, only 40% partial response rate was seen in 10 HES cases. FIP1L1-PDGFRA is a relatively infrequent but treatment-relevant mutation in primary eosinophilia that is indicative of an underlying systemic mastocytosis.
Division of Hematology and Internal Medicine, Laboratory Geentics and Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Animesh
A
Pardanani
Stephanie R
SR
Brockman
Sarah F
SF
Paternoster
Heather C
HC
Flynn
Rhett P
RP
Ketterling
Terra L
TL
Lasho
Ching-Liang
CL
Ho
Chin-Yang
CY
Li
Gordon W
GW
Dewald
Ayalew
A
Tefferi
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001549:Benzamides; D001853:Bone Marrow / Q000473:pathology; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D004802:Eosinophilia / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D006801:Humans; D000068877:Imatinib Mesylate; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion; D010879:Piperazines / Q000008:administration & dosage; D015995:Prevalence; D011743:Pyrimidines / Q000008:administration & dosage; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000235:genetics; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics*
D000970:Antineoplastic Agents; D001549:Benzamides; C121401:CHIC2 protein, human; D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011743:Pyrimidines; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors; D000068877:Imatinib Mesylate; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha