t(4;12)(q12;p13) PDGFRA/ETV6

2008-04-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology


Myeloproliferative disease with eosinophilia


Only one case to date, a 51 year old male patient.


The disease was rather indolent for over 7 years; imatinib was then started with significant resolution of symptoms, and the patient remains in cytogenetic remission 9 months later.

Genes Involved and Proteins

Gene name
PDGFRA (platelet-derived growth factor receptor, alpha polypeptide)
Protein description
Composed of an extracellular domain (the immunoglobulin-like motifs), a transmembrane domain, with an inhibitory juxtamembrane WW-like domain (Irusta et al., 2002), and an intracellular domain (kinase domain); receptor tyrosine kinase; forms homodimer, and heterodimer with PDGFRB; dimerization induces kinase domain activation, leading to the activation of intracellular signalling pathways (Kawagishi et al., 1995).
Somatic mutations
Hybrid genes between various partners and PDFRGA occur in chronic myeloid leukaemia-like diseases with eosinophilia, mostly chronic eosinophilic leukemia (CEL), a clonal hypereosinophilic syndrome. PDGFRA partners known so far are: STRN (2p24) (Curtis et al., 2007), FIP1L1 (4q12) (Cools et al., 2003, Pardanani et al., 2004), CDK5RAP2 (9q33) (Walz et al., 2006), KIF5B (10p11) (Score et al., 2006), ETV6 (12p13), herein described (Curtis et al., 2007), and BCR (22q11) (Baxter et al., 2002).
Mutations of platelet-derived growth factor receptor-alpha (PDGFRA) are observed in a subset of gastrointestinal stromal tumors (GISTs) (Heinrich et al., 2003).
Tumours with PDGFRA involvement are responsive to imatinib therapy (Cools et al., 2003; Debiec-Rychter et al., 2004).
Gene name
ETV6 (ets variant 6)
Protein description
Contains a HLH domain and a ETS-DNA binding domain; ETS-related transcription regulator.

Result of the Chromosomal Anomaly


5 ETV6-3 PDGFRA; Fusion between ETV6 intron 6 and PDGFRA intron 11; reciprocal product not found -> in frame fusion between ETV6 exon 6 and PDGFRA exon 12.


The N-term ETV6- C-term PDGFRA fusion protein retains most of ETV6, including the pointed domain and the ETS domain, fused to the WW-like domain and the kinase domain of PDGFRA; altough the WW-like domain is thought to act as an autoinhibitory element preventing kinase over-activation.

Highly cited references

Pubmed IDYearTitleCitations
295413912018Acute myeloid leukemia with t(4;12)(q12;p13): an aggressive disease with frequent involvement of PDGFRA and ETV6.3


Pubmed IDLast YearTitleAuthors
120239812002The t(4;22)(q12;q11) in atypical chronic myeloid leukaemia fuses BCR to PDGFRA.Baxter EJ et al
86399061996Rearrangement of the MLL gene confers a poor prognosis in childhood acute lymphoblastic leukemia, regardless of presenting age.Behm FG 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
175554502007Two novel imatinib-responsive PDGFRA fusion genes in chronic eosinophilic leukaemia.Curtis CE et al
150100692004Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group.Debiec-Rychter M et al
112417912001Reassessment of childhood B-lineage lymphoblastic leukemia karyotypes using spectral analysis.Elghezal H et al
125222572003PDGFRA activating mutations in gastrointestinal stromal tumors.Heinrich MC et al
121813112002Definition of an inhibitory juxtamembrane WW-like domain in the platelet-derived growth factor beta receptor.Irusta PM et al
85864211995Structure, organization, and transcription units of the human alpha-platelet-derived growth factor receptor gene, PDGFRA.Kawagishi J et al
84183691993Collaborative study of karyotypes in childhood acute lymphoblastic leukemias. Groupe Français de Cytogénétique Hématologique.
117934372002Similar patterns of genomic alterations characterize primary mediastinal large-B-cell lymphoma and diffuse large-B-cell lymphoma.Palanisamy N et al
152841182004FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia.Pardanani A et al
16591011991Relationship between chromosomal breakpoint and molecular rearrangement of T-cell antigen receptors in adult T-cell leukaemia.Sadamori N et al
23576891990Abnormalities involving chromosome 6 in newly diagnosed patients with non-Hodgkin's lymphoma. Nebraska Lymphoma Study Group.Schouten HC et al
164983882006Identification of a novel imatinib responsive KIF5B-PDGFRA fusion gene following screening for PDGFRA overexpression in patients with hypereosinophilia.Score J et al
168456592006Transient response to imatinib in a chronic eosinophilic leukemia associated with ins(9;4)(q33;q12q25) and a CDK5RAP2-PDGFRA fusion gene.Walz C et al



See also the t(4;12)(q11-q21;p13) with CHIC2.and ETV6 involvements in M0 acute myeloid leukaemia (M0-AML), keeping in mind that a t(4:12)(q13-21;p12-13) has also been described in B-cell acute lymphocytic leukaemia (ALL) (GFCH, 1993; Behm et al., 1996; Elghezal et al., 2001), B-cell non Hodgkins lymphoma (NHL) (Schouten et al., 1990; Palanisamy et al., 2002), and in a case of adult T-cell lymphoma/leukemia (Sadamori et al., 1991).


Jean-Loup Huret

t(4;12)(q12;p13) PDGFRA/ETV6

Atlas Genet Cytogenet Oncol Haematol. 2008-04-01

Online version: http://atlasgeneticsoncology.org/haematological/2137/t(4;12)(q12;p13)