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

Written2012-10Francois P Duhoux, Sandrine Medves, Laura Noël, Augustin Ferrant, Hélçne A Poirel, Jean-Baptiste Demoulin
Universite Catholique de Louvain, de Duve Institute, MEXP - UCL 74.30, avenue Hippocrate 75, BE-1200 Brussels, Belgium

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ICD-Morpho 9966/3 Myeloid and lymphoid neoplasms with PDGFRB rearrangement
ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
Atlas_Id 1612

Clinics and Pathology

Disease Myeloproliferative neoplasm with essential thrombocythemia
Note No detectable BCR-ABL transcript or JAK2 V617F mutation.
Epidemiology Found in one case of myeloproliferative neoplasm with severe thrombocythemia, in a 67-year-old male.
Clinics Thrombocythemia (platelets, 904 x 109/l) without prominent eosinophilia or neutrophilia.
Cytology Increased number of polymorphic megakaryocytes without any blast cells or dysplastic features; suggestive of myeloproliferative neoplasm, most likely essential thrombocythemia.
Treatment No response to hydroxyurea, complete remission with imatinib at the dose of 100 mg/day.
Evolution Complete remission (FU: 3 years).
Prognosis Unknown.


Cytogenetics Morphological 46,XY,t(5;9)(q31~32;p22~?24.3)[16]/46,XY[2].
Cytogenetics Molecular Disruption of PDGFRβ (5q31~32) and KANK1 (9p24.3) loci.
  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).
Probes RP11-130C19 and RP11-31F19.
Additional anomalies No.

Genes involved and Proteins

Gene NameKANK1 (KN motif and ankyrin repeat domains 1)
Location 9p24.3
Note Formerly: KANK, ANKRD15, KIAA0172.
Protein 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 NamePDGFRB (platelet-derived growth factor receptor, beta polypeptide)
Location 5q32
Protein Platelet-derived growth factors (PDGF) receptor, beta isoform. This receptor belongs to the receptor tyrosine kinase family (type III).

Result of the chromosomal anomaly

Hybrid gene
Description Exon 2 of KANK1 (ENST00000382293, Ensembl database, up to nucleotide 3020) is fused to exon 9 of PDGFRB (ENST00000261799, from nucleotide 1714).
Fusion Protein
  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.
Description 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).
Oncogenesis 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.

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.


Alterations des recepteurs du PDGF dans les hemopathies malignes.
Demoulin JB.
Louvain Medical, 2012, vol 131 (in press).
Kank proteins: structure, functions and diseases.
Kakinuma N, Zhu Y, Wang Y, Roy BC, Kiyama R.
Cell Mol Life Sci. 2009 Aug;66(16):2651-9. doi: 10.1007/s00018-009-0038-y. Epub 2009 May 12. (REVIEW)
PMID 19554261
Tyrosine kinase gene fusions in cancer: translating mechanisms into targeted therapies.
Medves S, Demoulin JB.
J Cell Mol Med. 2012 Feb;16(2):237-48. doi: 10.1111/j.1582-4934.2011.01415.x. (REVIEW)
PMID 21854543
KANK1, a candidate tumor suppressor gene, is fused to PDGFRB in an imatinib-responsive myeloid neoplasm with severe thrombocythemia.
Medves S, Duhoux FP, Ferrant A, Toffalini F, Ameye G, Libouton JM, Poirel HA, Demoulin JB.
Leukemia. 2010 May;24(5):1052-5. doi: 10.1038/leu.2010.13. Epub 2010 Feb 18.
PMID 20164854
Multiple oligomerization domains of KANK1-PDGFRb are required for JAK2-independent hematopoietic cell proliferation and signaling via STAT5 and ERK.
Medves S, Noel LA, Montano-Almendras CP, Albu RI, Schoemans H, Constantinescu SN, Demoulin JB.
Haematologica. 2011 Oct;96(10):1406-14. doi: 10.3324/haematol.2011.040147. Epub 2011 Jun 17.
PMID 21685469


This paper should be referenced as such :
Duhoux, FP ; Medves, S ; Noöl, L ; Ferrant, A ; Poirel, HA ; Demoulin, JB
t(5;9)(q32;p24) KANK1/PDGFRB
Atlas Genet Cytogenet Oncol Haematol. 2013;17(2):129-131.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(5;9)(q32;p24) KANK1/PDGFRB

External links

KANK1 (9p24.3) PDGFRB (5q32)

Mitelman databaset(5;9)(q32;p24)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9966/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9975/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databaseKANK1::PDGFRB [MCList]  KANK1 (9p24.3) PDGFRB (5q32)
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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indexed on : Fri Oct 8 16:36:37 CEST 2021

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