t(5;9)(q32;p24) KANK1/PDGFRB

2012-10-01   Francois P Duhoux , Sandrine Medves , Laura Noël , Augustin Ferrant , Hélçne A Poirel , Jean-Baptiste Demoulin 

1.Universite Catholique de Louvain, de Duve Institute, MEXP - UCL 74.30, avenue Hippocrate 75, BE-1200 Brussels, Belgium

Clinics and Pathology


No detectable BCR-ABL transcript or JAK2 V617F mutation.


Found in one case of myeloproliferative neoplasm with severe thrombocythemia, in a 67-year-old male.


Thrombocythemia (platelets, 904 x 109/l) without prominent eosinophilia or neutrophilia.


Increased number of polymorphic megakaryocytes without any blast cells or dysplastic features; suggestive of myeloproliferative neoplasm, most likely essential thrombocythemia.


No response to hydroxyurea, complete remission with imatinib at the dose of 100 mg/day.


Complete remission (FU: 3 years).




Atlas Image

Cytogenetics morphological


Cytogenetics molecular

Disruption of PDGFRβ (5q31~32) and KANK1 (9p24.3) loci.
Atlas Image
FISH analysis using the RP11-130C19 and RP11-31F19 probes. RP11-130C19 is split between the der(5) and the der(9), while RP11-31F19 is translocated to the der(5).


RP11-130C19 and RP11-31F19.

Additional anomalies


Genes Involved and Proteins

Gene name
KANK1 (KN motif and ankyrin repeat domains 1)
Formerly: KANK, ANKRD15, KIAA0172.
Protein description
Two KANK1 protein isoforms are encoded by different transcripts of the same gene: a long isoform of 1352 amino-acids and a short one 1194 aa, which is predominant in hematopoietic cells (Medves et al., 2010). Both isoforms have multiple N-terminal coiled-coil domains, which are included in the fusion with PDGFRB, and C-terminal ankyrin repeat domains (Kakinuma et al., 2009).
Gene name
PDGFRB (platelet-derived growth factor receptor, beta polypeptide)
Protein description
Platelet-derived growth factors (PDGF) receptor, beta isoform. This receptor belongs to the receptor tyrosine kinase family (type III).

Result of the Chromosomal Anomaly


Exon 2 of KANK1 (ENST00000382293, Ensembl database, up to nucleotide 3020) is fused to exon 9 of PDGFRB (ENST00000261799, from nucleotide 1714).
Atlas Image
Structure of PDGFRB, KANK1 and the KANK1-PDGFRB fusion. See text for details. KOD, KANK1 oligomerization domain. Adapted from Demoulin et al., 2012 and Medves et al., 2012.


The fusion protein contains the first 741 residues of KANK1 fused to the last 692 residues of PDGFRB (Medves et al., 2010). This includes several coiled-coil domains of KANK1 and the fifth immunoglobulin-like domain, the transmembrane domain and the kinase domain of PDGFRB. The deletion of the immunoglobulin-like domain does not affect the oncogenic activity of the fusion (Medves et al., 2010). By contrast, deletion of the coiled-coil domains prevents cell transformation and signaling via STAT5 and MAP kinases (Medves et al., 2011). Our data suggest that KANK1-PDGFRB adopts a trimeric and multimeric conformation (Medves et al., 2011).


This fusion protein induces the proliferation of Ba/F3 cells (Medves et al., 2010) and CD34+ human progenitors (Medves et al., 2011).
The fusion was identified in thrombocythemia, which is associated with JAK2 mutations or indirect activation of JAK2 by mutated thrombopoietin receptors (c-MPL). In the present case, no JAK2 activation was detected in cells expressing KANK1-PDGFRB and these cells are not sensitive to JAK inhibitors (Medves et al., 2011). Instead, they are highly sensitive to imatinib.

Highly cited references

Pubmed IDYearTitleCitations
216854692011Multiple oligomerization domains of KANK1-PDGFRβ are required for JAK2-independent hematopoietic cell proliferation and signaling via STAT5 and ERK.11


Pubmed IDLast YearTitleAuthors
195542612009Kank proteins: structure, functions and diseases.Kakinuma N et al
218545432012Tyrosine kinase gene fusions in cancer: translating mechanisms into targeted therapies.Medves S et al
201648542010KANK1, a candidate tumor suppressor gene, is fused to PDGFRB in an imatinib-responsive myeloid neoplasm with severe thrombocythemia.Medves S et al
216854692011Multiple oligomerization domains of KANK1-PDGFRβ are required for JAK2-independent hematopoietic cell proliferation and signaling via STAT5 and ERK.Medves S et al


Fusion gene

KANK1/PDGFRB KANK1 (9p24.3) PDGFRB (5q32) M t(5;9)(q32;p24)


Francois P Duhoux ; Sandrine Medves ; Laura Noël ; Augustin Ferrant ; Hélçne A Poirel ; Jean-Baptiste Demoulin

t(5;9)(q32;p24) KANK1/PDGFRB

Atlas Genet Cytogenet Oncol Haematol. 2012-10-01

Online version: http://atlasgeneticsoncology.org/haematological/1612/t(5;9)(q32;p24)