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.
Pardanani
Animesh
A
Division of Hematology and Internal Medicine, Laboratory Geentics and Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Brockman
Stephanie R
SR
Paternoster
Sarah F
SF
Flynn
Heather C
HC
Ketterling
Rhett P
RP
Lasho
Terra L
TL
Ho
Ching-Liang
CL
Li
Chin-Yang
CY
Dewald
Gordon W
GW
Tefferi
Ayalew
A
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