del(4)(q12q12) FIP1L1/PDGFRA

2014-05-01   Soad Al Bahar , Adriana Zamecnikova 

1.Kuwait Cancer Control Center, Laboratory of Cancer Genetics, Department of Hematology, Shuwaikh, 70653, Kuwait

Clinics and Pathology


An interstitial deletion del(4)(q12q12) generating a FIP1L1-PDGFRA fusion gene is observed in diverse eosinophilia-associated hematologic disorders like hyperseosinophilic syndrome (HES), systemic mastocytosis (SM) and chronic eosinophilic leukemia (CEL). The updated WHO classification distinguishes these myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 as chronic eosinophilic leukemia (CEL) not otherwise specified (NOS); lymphocyte-variant hypereosinophilia and idiopathic hypereosinophilic syndrome (HES) (Gleich and Leiferman, 2009; Gotlib, 2014). Occasionally, the FIP1L1-PDGFRA fusion can be identified in patients with acute myeloid leukemia or B-cell or T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma and sporadically in myeloid sarcoma (Metzgeroth et al., 2007; Tang et al., 2012).

Phenotype stem cell origin

FIP1L1-PDGFRA rearrangement has been found in a variety of cell lineages (neutrophils, monocytes, eosinophils, CD34+ cells, mast cells and even lymphoid) consistent with an origin in an hematopoietic stem cells or early progenitors progenitor (Gotlib and Cools, 2008).


The cause of FIP1L1-PDGFRA associated hypereosinophilic syndrome is unknown as well as its association with predominantly male sex.


FIP1L1-PDGFRA (+) eosinophilias are considered to be rare entities; however the incidence rates for molecularly defined eosinophilic disorders are not known. Data support a FIP1L1-PDGFRA fusion incidence of approximately 10-20% among patients presenting with idiopathic hypereosinophilia (Gotlib and Cools, 2008). However, in unselected patients with eosinophilia only 3% of were found to carry the FIP1L1-PDGFRA fusion (Pardanani et al., 2004; Pardanani et al., 2006).


Characteristic feature of PDGFRA-associated disorders is eosinophil overproduction in the bone marrow resulting in increased blood eosinophils. Marked and sustained eosinophilia eventually leads to eosinophilic infiltration and functional damage of peripheral organs, most commonly the heart, skin, lungs, or nervous system. Patients often present with hepatomegaly or splenomegaly hypercellular bone marrows with myelofibrosis, increased number of neutrophils and/or mast cells. Serum B12 and tryptase levels may be significantly elevated (Vandenberghe et al., 2004; Gleich and Leiferman, 2009).


FIP1L1-PDGFRA associated hypereosinophilic disorders are sensitive to treatments with tyrosine kinase inhibitors such as imatinib mesylate (imatinib). Imatinib is the first-line therapy for patients with abnormalities of PDGFRA; however chronic eosinophilic leukemia with FIP1L1-PDGFRA is likely to be responsive also to dasatinib, nilotinib, sorafenib and midostaurin (PKC412) (Lierman et al., 2009).


Patients with hypereosinophilic syndrome historically carried a poor prognosis before the successful therapeutic application of tyrosine kinase inhibitors. Targeted therapy has dramatically changed the prognosis of patients carrying the FIP1L1-PDGFRA fusion which show an excellent response to low-dose imatinib. Treatment with low-dose imatinib (100 mg/d) produced complete and durable responses with normalization of eosinophilia. Importantly, these remissions appear to be durable with continued imatinib therapy in a high proportion of patients (Barraco et al., 2014). Acquired resistance is exceedingly rare; the T674I mutation in the ATP-binding region of PDGFRA (mutation of the threonine at position 674) is the most common. Interestingly, the T674I mutation that is analogous to the T315I mutation of BCR-ABL1 in chronic myeloid leukemia also confers imatinib resistance (Cools et al., 2003; Jain et al., 2013). For refractory disease, interferon-a may be a therapeutic option.



The cryptic interstitial deletion on chromosome band 4q12 leading to FIP1L1-PDGFRA fusion is quite unique as it is generated by a cryptic chromosomal deletion, rather than a translocation (Gotlib and Cools, 2008).

Cytogenetics morphological

Because FIP1L1-PDGFRA is generated by a cryptic deletion at 4q12 that is only 800 kb in size, it remains undetected with standard cytogenetics. Therefore; most of the patients with the fusion have an apparently normal karyotype. Occasional patients have had a chromosomal rearrangement with a 4q12 breakpoint, such as t(1;4)(q44;q12), which ultimately led to the identification of the fusion gene or t(4;10)(q12;p11) (Cools et al., 2003; Gotlib et al., 2004).

Cytogenetics molecular

One of the best techniques to detect the presence of the FIP1L1-PDGFRA fusion gene is using triple-color FISH probes hybridizing to the region between the FIP1L1 and PDGFRA genes incorporating the CHIC2 (cysteine-rich hydrophobic domain 2) gene. A more sensitive technique is the use of reverse-transcription polymerase chain reaction (RT-PCR) (La Starza et al., 2005) or quantitative RT-PCR methods, used for monitoring therapy response to tyrosine kinase inhibitors.
Atlas Image
Figure 1. Detection of the del(4)(q12q12) by fluorescence in situ hybridization using the LSI FIP1L1-CHIC2-PDGFRA Triple-Color, split assay (Abott Molecular; Vysis, Denver US) on a metaphase (A) and interphases (B). This probe is designed as a deletion probe when absence of the CHIC2 region is observed as loss of a red signal (arrows) from the co-localized green/blue signal, indicative of the presence of this specific deletion that leads to FIP1L1-PDGFRA fusion on one of the chromosomes 4.


A few other variant PDGFRA fusion genes have been described: t(4;22)(q12;q11)/BCR-PDGFRA, t(2;4)(p24;q12)/STRN-PDGFRA, ins(9;4)(q33;q12q25)/CDK5RAP2-PDGFRA, complex karyotype/KIF5B-PDGFRA and t(4;12)(q12;p13)/ETV6-PDGFRA (Gleich and Leiferman, 2009). The involvement of FIP1L1 was described in a t(4;17)(q12;q21) with FIP1L1/RARA fusion in a patient with juvenile myelomonocytic leukemia (Shah et al., 2014).

Genes Involved and Proteins

Gene name
PDGFRA (platelet-derived growth factor receptor, alpha polypeptide)
platelet-derived growth factor receptor, alpha polypeptide
Dna rna description
PDGFRA contains 23 exons spanning about 65 kb. The gene encodes a cell surface tyrosine kinase receptor. An important paralog of PDGFRA is FLT4.
Protein description
1089 amino acids; PDGFA belongs to a family of receptor tyrosine kinases that include PDGFRA and PDGFRB that have intracellular tyrosine kinase activity that binds members of the platelet-derived growth factor family. It plays an essential role in the regulation of embryonic development, organ development, wound healing, angiogenesis and chemotaxis; role in the differentiation of bone marrow-derived mesenchymal stem cells, cell proliferation and survival (Hsieh et al., 1991; Kawagishi et al., 1995). PDGFRA is involved in the pathogenesis of various disorders, including cancer.
Gene name
FIP1L1 (factor interacting with PAPOLA and CPSF1)
factor interacting with PAPOLA and CPSF1
Dna rna description
4 distinct isoforms; alternative splicing results in multiple transcript variants.
Protein description
pre-mRNA 3-end-processing factor; 520 amino acids. FIP1 belongs to the FIP1 family. It has RNA binding protein kinase activity as a component of cleavage and polyadenylation specificity factor (CPSF) complex. Plays a key role in polyadenylation of the 3 end of mRNA precursors and in the transcriptional process. FIP1L1 is predicted to be under the control of a ubiquitous promoter. Many additional functions of the protein are largely unknown (Gotlib et al., 2004).

Result of the Chromosomal Anomaly

Atlas Image
Figure 2. Model of the involvement of PDGFRA-FIP1L1 fusion gene in the pathogenesis of hypereosinophilic disorders. A cryptic deletion on chromosome 4 brings the normally distant PDGFRA and FIP1L1 genes into close proximity, generating a fused gene. Fusion of FIP1L1 to the PDGFRA protein results in a constitutive kinase activation of PDGFRA with transforming potential that may lead to eosinophilic disorders. Administration of the kinase inhibitor such as imatinib is highly effective molecularly targeted therapy for this group of patients.


In-frame fusion of the 5 part of FIP1L1 to the 3 part of PDGFRA.
The FIP1L1-PDGFRA protein is made by the first twelve exons of FIP1L1 and from truncated exon 12 (containing the last 17 amino acids) to exon 23 of PDGFRA. The FIP1L1-PDGFRA fusion protein is a constitutively activated tyrosine kinase that joins the first 233 amino acids of FIP1L1 to the last 523 amino acids of PDGFRA (Gotlib and Cools, 2008).


5FIP1L1-3PDGFRA; no reciprocal PDGFRA-FIP1L1 fusion gene can be detected as the fusion is the consequence of an interstitial deletion and not a reciprocal translocation. As the normal splice site at 5 part of exon 12 of PDGFRA is deleted, cryptic splice sites in FIP1L1 introns or within exon 12 of PDGFRA are used to generate in-frame FIP1L1-PDGFRA fusions (Gotlib and Cools, 2008).
Atlas Image
Figure 3. Generation of the FIP1L1-PDGFRA fusion protein. Splicing of FIP1L1 exons to the truncated exon 12 of PDGFRA results in disruption of the autoinhibitory juxtamembrane domain of PDGFRA. FIP1L1-PDGFRA expression became under control of the ubiquitous FIP1L1 promoter leading to dysregulated tyrosine kinase activity. NLS indicates nuclear localization signal; TM, transmembrane region; JM, juxtamembrane region. Adapted from Cools et al., 2003; Vandenberghe et al., 2004; Gotlib and Cools, 2008; Gleich and Leiferman, 2009.


An interstitial deletion on chromosome 4q12 site brings the normally distant PDGFRA and FIP1L1 genes into proximity generating a hybrid FIP1L1-PDGFRA gene. In the translated protein, the juxtamembrane domain of PDGFRA that is known to serve an autoinhibitory function is truncated and became under control of the ubiquitous FIP1L1 promoter resulting in its constitutive kinase activation. Dysregulated tyrosine kinase activity leads to proliferation of multiple myeloid lineages via activation of several pathways. The STAT1/3 and STAT5 (signal transducers and activators of transcription) transcriptional factors appear to be activated either directly or via interaction with JAK (Janus activated kinase) pathways. However, the exact mechanism, by which FIP1L1-PDGFR affects the development of HES/CEL and why preferentially affects eosinophils remains unclear. Mouse models of FIP1L1-PDGFRA induced disease revealed that FIP1L1-PDGFRA expression induce a myeloproliferative phenotype without eosinophilia. Therefore, it is likely that FIP1L1-PDGFRA expression alone is not sufficient to cause eosinophilia and additional processes such as cooperation with nuclear factor-kB and IL-5 signaling are required in differentiation towards the eosinophil lineage (Yamada et al., 2006; Montano-Almendras et al., 2012).

Highly cited references

Pubmed IDYearTitleCitations
264753672016Hypereosinophilic Syndrome.36
267978022016Clinical features predict responsiveness to imatinib in platelet-derived growth factor receptor-alpha-negative hypereosinophilic syndrome.22
329567562020Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial.20
260172882015KIT D816V and JAK2 V617F mutations are seen recurrently in hypereosinophilia of unknown significance.13
280108952017Platelet-derived growth factor receptors (PDGFRs) fusion genes involvement in hematological malignancies.10
262098912015Evaluation and Differential Diagnosis of Persistent Marked Eosinophilia.10
262099002015Management of Hypereosinophilic Syndromes.10
271208082016Long-term outcomes of imatinib in patients with FIP1L1/ PDGFRA associated chronic eosinophilic leukemia: experience of a single center in China.9
337377042021Venous thrombosis and predictors of relapse in eosinophil-related diseases.8
329035982020S100A8 and S100A9 Promote Apoptosis of Chronic Eosinophilic Leukemia Cells.8
291701722017Eosinophilic myocarditis as a first presentation of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).8
293033682018Imatinib for the treatment of hypereosinophilic syndromes.7
270215542016Generation of the Fip1l1-Pdgfra fusion gene using CRISPR/Cas genome editing.7
322472632020GZD824 as a FLT3, FGFR1 and PDGFRα Inhibitor Against Leukemia In Vitro and In Vivo.6
298962032018Efficacy and Safety of Mepolizumab (Anti-Interleukin-5) Treatment in Gleich's Syndrome.6
267974292016Diagnostic challenges in the work up of hypereosinophilia: pitfalls in bone marrow core biopsy interpretation.6
266634002016Next generation sequencing of myeloid neoplasms with eosinophilia harboring the FIP1L1-PDGFRA mutation.6
295382002018Loeffler endocarditis as a rare cause of heart failure with preserved ejection fraction: A case report and review of literature.5
286733932017Tyrosine Kinase Inhibitors in the Treatment of Eosinophilic Neoplasms and Systemic Mastocytosis.5
284407142017Hypereosinophilic syndrome: endomyocardial biopsy versus echocardiography to diagnose cardiac involvement.5
271728732016Early-Stage Loeffler's Endocarditis with Isolated Right Ventricular Involvement: Management, Long-Term Follow-Up, and Review of Literature.5
290294062017Lyn mediates FIP1L1-PDGFRA signal pathway facilitating IL-5RA intracellular signal through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex in CEL.5
330489492020Aberrant expression of NKL homeobox genes HMX2 and HMX3 interferes with cell differentiation in acute myeloid leukemia.4
264572332015Refractory myeloid sarcoma with a FIP1L1-PDGFRA rearrangement detected by clinical high throughput somatic sequencing.4
257619342015F604S exchange in FIP1L1-PDGFRA enhances FIP1L1-PDGFRA protein stability via SHP-2 and SRC: a novel mode of kinase inhibitor resistance.4
343046032021FIP1L1-PDGFRA-Associated Hypereosinophilic Syndrome as a Treatable Cause of Watershed Infarction.3
340528712021Eosinophils and eosinophil-associated disorders: immunological, clinical, and molecular complexity.3
319951562020Treatment-free remission in FIP1L1-PDGFRA-positive myeloid/lymphoid neoplasms with eosinophilia after imatinib discontinuation.3
302107452018The Spectrum of Hypereosinophilia and Associated Clonal Disorders - A Real-World Data Based on Combined Retrospective and Prospective Analysis from a Tropical Setting.3
299775372018FIP1L1-PDGFRA fusion-negative hypereosinophilic syndrome with uncommon cardiac involvement responding to imatinib treatment: A case report.3
289541052017Episodic angioedema associated with eosinophilia.3
279600342017Leukemogenic kinase FIP1L1-PDGFRA and a small ubiquitin-like modifier E3 ligase, PIAS1, form a positive cross-talk through their enzymatic activities.3
278039152016Idiopathic hypereosinophilic syndrome presenting with severe vasculitis successfully treated with imatinib.3
327207002020Epidemiology, clinical picture and long-term outcomes of FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia: Data from 151 patients.2
326560112020Hypereosinophilic Syndrome, Multiorgan Involvement and Response to Imatinib.2
318541042020Frequent false-negative FIP1L1-PDGFRA FISH analyses of bone marrow samples from clonal eosinophilia at diagnosis.2
286514272018Loeffler endocarditis in chronic eosinophilic leukemia with FIP1L1/PDGFRA rearrangement: full recovery with low dose imatinib.2
295876712018Coexisting of bone marrow fibrosis, dysplasia and an X chromosomal abnormality in chronic neutrophilic leukemia with CSF3R mutation: a case report and literature review.2
290892592017Trisubstituted purine inhibitors of PDGFRα and their antileukemic activity in the human eosinophilic cell line EOL-1.2
290256012017A neoplasm with FIP1L1-PDGFRA fusion presenting as pediatric T-cell lymphoblastic leukemia/lymphoma without eosinophilia.2
307559502017When Hypereosinophilia Leads to Stroke.2
271649402016Severe Prolonged Cough as Presenting Manifestation of FIP1L1-PDGFRA+ Chronic Eosinophilic Leukaemia: A Widely Ignored Association.2
264309102016Imatinib discontinuation for hypereosinophilic syndrome harboring the FIP1L1-PDGFRA transcript.2
259238372015Generalized Eruptive Histiocytosis Associated With FIP1L1-PDGFRA-Positive Chronic Eosinophilic Leukemia.2
258301342015Chronic eosinophilic leukemia with a FIP1L1-PDGFRA rearrangement: Two case reports and a review of Korean cases.2
257547212015Hypereosinophilic disorders.2
245762192015Newly identified phenotypes in a FIP1L1/PDGFRA-associated paediatric HES patient: thrombocytosis, mHPA, young stroke and blindness.2
350055892021Diagnosis and treatment of eosinophilic myocarditis.1
334590362021Successful Long-Term Control of the Syndrome of Episodic Angioedema With Eosinophilia (Gleich Syndrome) With Low-Dose Imatinib Mesylate and Prednisone.1
323609182020FIP1L1-PDGFRA-Positive Hypereosinophilia Presenting with Bilateral Extracranial Carotid Artery Aneurysms.1
322696332020Imatinib therapy in acute myeloid leukemia with DEK-NUP214 and FIP1L1-PDGFRA rearrangement: A case report.1
316913592020LCP1 triggers mTORC2/AKT activity and is pharmacologically targeted by enzastaurin in hypereosinophilia.1
315140192019Activity of 2,6,9-trisubstituted purines as potent PDGFRα kinase inhibitors with antileukaemic activity.1
322333222019[Hypereosinophilic syndromes].1
308073972019Myeloid Neoplasm With Eosinophilia and FIP1L1-PDGFRA Rearrangement Treated With Imatinib Mesylate: A Pediatric Case With Long-term Follow-up.1
310367332019Hypereosinophilia and severe bone disease in an African child: an unexpected diagnosis.1
293108332018Myeloid neoplasm with eosinophilia associated with isolated extramedullary FIP1L1/PDGFRA rearrangement.1
273911912016Pathological fracture due to lytic lesion caused by a myeloid neoplasm with FIP1L1-PDGFRA.1
264920572015Successful Heart Transplantation for Unreversible Endomyocardial Fibrosis Related to FIP1L1-PDGFRA Chronic Eosinophilic Leukemia.1
359635222022Fusion Gene Detection and Quantification by Asymmetric Capture Sequencing (aCAP-Seq).0
359339112022Imatinib responsive erythrocytosis in a patient with FIP1L1::PDGFRA rearranged myeloid neoplasm with hypereosinophilia - Another manifestation of a stem cell neoplasm.0
357220862022Case Report: Multimodal Imaging Guides the Management of an Eosinophilic Leukemia Patient With Eosinophilic Myocarditis and Intracardiac Thrombus.0
354548922022Next-Generation DNA Sequencing-Based Gene Panel for Diagnosis and Genetic Risk Stratification in Onco-Hematology.0
353818112022"Likely to be missed if unsuspected": FIP1L1-PDGFRA positive myeloid neoplasm in a patient with nodal T-lineage lymphoblastic lymphoma.0
350023482021Pruritus as a Presenting Symptom of FIP1L1-PDGFRA-Positive Chronic Eosinophilic Leukemia.0
349174982021Case Report: Evolution of KIT D816V-Positive Systemic Mastocytosis to Myeloid Neoplasm With PDGFRA Rearrangement Responsive to Imatinib.0
345542192021Myocarditis, kidney injury, and hypereosinophilia: FIP1L1-PDGFRA-positive myeloid/lymphoid neoplasm with eosinophilia.0
340452022021FIP1L1-PDGFRA fusion gene in a patient with asthma and rhinitis.0
338868122021Episodic angioedema with eosinophilia (Gleich's syndrome) associated with urticarial vasculitis: a coincidence or a novel clinical entity?0
348660842021[Emergence of mutation in the colony-stimulating factor 3 receptor gene during follow-up of unclassifiable myeloproliferative neoplasm].0
335851392021A Case of Chronic Eosinophilic Leukemia in a Patient With Recurrent Cough, Dyspnea, and Eosinophilia.0
334458552020[Acute myeloid leukemia with FIP1L1-PDGFRA fusion gene treated with imatinib: a case report and literature review].0
331960112020Sustained Complete Molecular Remission With Imatinib Monotherapy in a Child Presenting With Blast Phase FIP1L1-PDGFRA-Associated Myeloid Neoplasm With Eosinophilia.0
323644092020Progressive multifocal leukoencephalopathy responsive to withdrawal of imatinib in a patient with FIP1L1-PDGFRA positive myeloid neoplasm.0
324253952020Paratrabecular myelofibrosis and occult mastocytosis are strong morphological clues to suspect FIP1L1-PDGFRA translocation in hypereosinophilia.0
323111582020A myeloid neoplasm with FIP1L1-PDGFRA presenting as acute myeloid leukemia.0
321252942020Exquisite response to imatinib mesylate in FIP1L1-PDGFRA-mutated hypereosinophilic syndrome: a 12-year experience of the Polish Hypereosinophilic Syndrome Study Group.0
322246792020The Efficacy of Imatinib Mesylate in the Treatment of a Rare Lytic Bone Lesion Caused by Hypereosinophilic Syndrome/Chronic Eosinophilic Leukemia: A Case Report.0
320021882020Ascites in a young male: idiopathic FIP1L1-PDGFRA-negative hypereosinophilic syndrome.0
319144672020[Complete remission of Loeffler's endocarditis with Imatinib in a myeloid and lymphoid neoplasm associated with eosinophilia].0
314501162019A complex and cryptic intrachromosomal rearrangement generating the FIP1L1_PDGFRA in adult acute myeloid leukemia.0
317373822019An Intriguing Case of Eosinophilia with FIP1L1/PDGFRA Rearrangement Who Presented as Thrombotic Thrombocytopenic Purpura.0
310210022019Pemphigus-like hypereosinophilic syndrome with FIP1L1-PDGFRA fusion gene: A challenging and uncommon clinical presentation.0
303595452019Identification of a novel PDGFRA point mutation at p.P6L as a potential molecular target of imatinib in an eosinophilia patient showing genetic heterogeneity.0
297146512018Hypereosinophilic syndrome preceding a diagnosis of B-cell lymphoma.0
299242262018Case for diagnosis. Erythroderma as manifestation of hypereosinophilic syndrome.0
295231792018A young female presenting with heart failure secondary to eosinophilic myocarditis: a case report and review of the literature.0
301175272018Speckle tracking and global longitudinal strain in endomyocardial infiltration during FIP1L1-PDGFRA chronic eosinophilic leukaemia.0
288853612017Angioimmunoblastic T-cell lymphoma and hypereosinophilic syndrome with FIP1L1/PDGFRA fusion gene effectively treated with imatinib: A case report.0
283740412017Imatinib Treatment of Lymphomatoid Papulosis Associated with Myeloproliferative Hypereosinophilic Syndrome Presenting the FIP1L1-PDGFRA Fusion Gene.0
283475832017Hypereosinophilic Syndrome as a Rare Cause of Reversible Biventricular Heart Failure.0
281866042017[Clinical and genetic features of a patient with myeloid neoplasm in association with PDGFRA and EVI1 gene rearrangements].0
280289042016Imatinib-sensitive myeloid neoplasm with low allele burden of FIP1L1-PDGFRA fusion gene in an elderly patient.0
269752262016Management of Loeffler's Endocarditis With Bivalvular Involvement and a FIP1L1/PDGFRA-Negative Mutation.0
278466622016[The Lymphoid Variant of HES (L-HES) as Differential Diagnose of Severe Asthma in Childhood].0
277221332016Chronic eosinophilic leukemia with FIP1L1-PDGFRA rearrangement.0
266665782016A case of myeloid neoplasm with FIP1L1-PDGFRA rearrangement without marked peripheral blood eosinophilia.0
262674132015[The Hypereosinophilic Syndromes in Childhood].0
254215402015CD30+ clonal T-cell lymphoid proliferation of the skin in a patient with hypereosinophilic syndrome.0
257864562015Diagnostic challenges during pretreatment long-term follow-up in a patient with FIP1L1-PDGFRA-positive eosinophilia.0


Pubmed IDLast YearTitleAuthors
244606802014Complete and long-lasting cytologic and molecular remission of FIP1L1-PDGFRA-positive acute eosinophil myeloid leukaemia, treated with low-dose imatinib monotherapy.Barraco D et al
126603842003A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome.Cools J et al
192433812009The hypereosinophilic syndromes: current concepts and treatments.Gleich GJ et al
188432832008Five years since the discovery of FIP1L1-PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias.Gotlib J et al
245778082014World Health Organization-defined eosinophilic disorders: 2014 update on diagnosis, risk stratification, and management.Gotlib J et al
17114351991Chromosomal localization of the gene for AA-type platelet-derived growth factor receptor (PDGFRA) in humans and mice.Hsieh CL et al
242039302013Imatinib therapy in a patient with suspected chronic neutrophilic leukemia and FIP1L1-PDGFRA rearrangement.Jain N et al
85864211995Structure, organization, and transcription units of the human alpha-platelet-derived growth factor receptor gene, PDGFRA.Kawagishi J et al
159213742005The hypereosinophilic syndrome: fluorescence in situ hybridization detects the del(4)(q12)-FIP1L1/PDGFRA but not genomic rearrangements of other tyrosine kinases.La Starza R et al
175919422007A case of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia with a rare FIP1L1 breakpoint.Lambert F et al
192123372009FIP1L1-PDGFRalpha D842V, a novel panresistant mutant, emerging after treatment of FIP1L1-PDGFRalpha T674I eosinophilic leukemia with single agent sorafenib.Lierman E et al
173775852007Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma.Metzgeroth G et al
222718942012ETV6-PDGFRB and FIP1L1-PDGFRA stimulate human hematopoietic progenitor cell proliferation and differentiation into eosinophils: the role of nuclear factor-κB.Montano-Almendras CP et al
164060162006FIP1L1-PDGFRA in eosinophilic disorders: prevalence in routine clinical practice, long-term experience with imatinib therapy, and a critical review of the literature.Pardanani A et al
246697612014Discovery of imatinib-responsive FIP1L1-PDGFRA mutation during refractory acute myeloid leukemia transformation of chronic myelomonocytic leukemia.Shah S et al
227226482012Complete response of myeloid sarcoma with FIP1L1-PDGFRA -associated myeloproliferative neoplasms to imatinib mesylate monotherapy.Tang TC et al
149735042004Clinical and molecular features of FIP1L1-PDFGRA (+) chronic eosinophilic leukemias.Vandenberghe P et al
164183252006The FIP1L1-PDGFRA fusion gene cooperates with IL-5 to induce murine hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)-like disease.Yamada Y et al


Fusion gene



Soad Al Bahar ; Adriana Zamecnikova

del(4)(q12q12) FIP1L1/PDGFRA

Atlas Genet Cytogenet Oncol Haematol. 2014-05-01

Online version: