Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

del(5)(q32q33) EBF1::PDGFRB

Written2016-10Gauthier Decool, Benoît Ducourneau, Nicolas Duployez, Catherine Roche-Lestienne
CHU Lille, Laboratoire d'Hématologie, Centre de Biologie-Pathologie (GD, BD, ND), INSERM UMR-S 1172, Institut de Recherche sur le Cancer de Lille (ND, CRL), CHU Lille, Institut de Génétique Médicale, Hôpital Jeanne de Flandre (CRL), F-59000, France;;;;

Abstract Review on del(5)(q32q33) EBF1/PDGFRB fusion with clinical data and genes involved.

Keywords EBF1, PDGFRB; fusion transcript, tyrosine kinase, BCR/ABL1-like; chromosome 5

(Note : for Links provided by Atlas : click)


ICD-Topo C420,C421,C424
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id 1712
Note According to the recent revision to the WHO classification of myeloid neoplasm and acute leukemia (Arber et al, Blood, 2016), BCP-ALL with EBF1/PDGFRB fusion should be referred as 'BCR/ABL1-like B-lymphoblastic leukemia/lymphoma' (provisional entity). BCR/ABL1-like ALL (or Ph-like ALL) lack the BCR/ABL1 fusion but demonstrate a gene expression profile and a poor outcome similar to BCR/ABL1-positive ALL (den Boer et al, Lancet Oncol, 2009). Kinase activating alterations (including the EBF1/PDGFRB fusion) are a hallmark of the disease and could be found in virtually all patients with BCR/ABL1-like ALL (Roberts et al, Cancer Cell 2012; Roberts et al, N Engl J Med, 2014).

Clinics and Pathology

Disease B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
Phenotype / cell stem origin B-cell precursor
Epidemiology The EBF1/PDGFRB fusion accounts for about 0.5% of BCP-ALL, 3% of B-other ALL and 8% of BCR-ABL1-like ALL (Schwab et al, Blood, 2016). The prevalence of EBF1/PDGFRB-positive ALL is expected to increase with age in parallel with the prevalence of BCR-ABL1-like ALL which ranges from 10% in children to 20% in adolescent and near 30% in young adults.
Clinics About 25 cases have been reported so far (Schwab et al, Blood, 2016; Lengline et al, Haematologica 2013; Weston et al, J Clin Oncol, 2013, Robert et al, Cancer Cell 2012; Roberts et al, N Engl J Med 2014). Patients were aged from 4 to 20y (median: 12y) and often displayed high leukocyte counts at presentation, especially in IKZF1-deleted cases.
Treatment The detection of the EBF1/PDGFRB fusion is critical since the fusion protein could be targeted by tyrosine kinase inhibitors (TKIs) such as imatinib of dasatinib. Importantly, recent reports have shown successful TKI therapy even in patients refractory to conventional therapy.
Evolution Patients with EBF1/PDGFRB-positive ALL are characterized by high levels of minimal residual disease and a higher tendency of relapse compared with other ALL subtypes. However, there is evidence of durable remission especially after intensive chemotherapy. Finally, considering several reports, the use of TKIs should be assessed in EBF1/PDGFRB-positive patients and could decrease relapse rate and avoid the need of intensive chemotherapy.


Note The EBF1/PDGFRB is usually not seen by conventional karyotype.
Cytogenetics Morphological Karyotype is normal by conventional cytogenetics in half of the cases. The EBF1/PDGFRB fusion usually results from a cryptic 5q33 deletion requiring the use of fluorescent in situ hybridization (FISH), comparative genomic hybridization (CGH) or single nucleotide polymorphism (SNP)-array. Rarely, it could result from a t(5;5)(q32;q33.3) translocation or a complex 5q rearrangement. Additional cytogenetic events could include trisomy 5 (containing the EBF1 and PDGFRB genes) or abnormal chromosome 5, deletion of the short arm of chromosome 9 as well as atypical aberrations.
Cytogenetics Molecular The EBF1/PDGFRB fusion results most often from a del(5)(q32q33.3) of about 8.6 Mb with breakpoints located within EBF1 and PDGFRB.
Interestingly, multiplex ligation dependent probe amplification (MLPA) (SALSA MLPA kit P335 IKZF1, MRC Holland) shows deletion of EBF1 exon 16 in more than 70% of EBF1/PDGFRB-positive ALL (Schwab et al, Blood, 2016). Among the genes tested by MLPA, PAX5, IKZF1 and/or CDKN2A/CDKN2B are often deleted.
  SNP-array karyotyping (Cytoscan HD, Affymetrix) showing a 5q33 deletion delimited by the PDGFRB and EBF1 genes (picture from Chromosome Analysis suite®).

Genes involved and Proteins

Note The 5q33 deletion (more rarely t(5;5) translocation) leads to the fusion of EBF1 and PDGFRB.
Gene NamePDGFRB (platelet-derived growth factor receptor, beta polypeptide)
Location 5q32
Dna / Rna The PDGFRB gene contains 22 exons.
Protein PDGFRB is a cell surface tyrosine kinase (TK) receptor for the platelet-derived growth factor family. PDGFRB belongs to the type III group of TKs (which also include , and (the M-CSF receptor)) and consists of five extracellular immunoglobulin-like domains, a single-spanning transmembrane domain and an intracellular kinase domain, split in two domains by a kinase insert. The TK domain is normally activated in response to ligand binding and receptor dimerization. PDGFRB is involved in embryonic development and modulation of hematopoietic cell functions.
Gene NameEBF1 (early B-cell factor 1)
Location 5q33.3
Dna / Rna The EBF1 gene contains 16 exons.
Protein EBF1 is a transcription factor critical for B cell differentiation, signal transduction and function. EBF family proteins consist of an N-terminal DNA-binding domain including a zinc binding motif, designated as "zinc-knuckle", a transcription factor immunoglobulin (TIG) domain and a helix-loop-helix domain, followed by a C-terminal transactivation domain.

Result of the chromosomal anomaly

Hybrid gene
Description The hybrid gene The fusion usually involved PDGFRB exon 11 fused to EBF1 exon15 (rarely alternative breakpoints involving EBF1 exon 14).
Detection FISH detection with PDGFRB and EBF1 breakapart probes or identification of the EBF1/PDGFRB transcript fusion by ligation-dependent reverse transcriptase-polymerase chain reaction (LD-RTPCR).
Fusion Protein
  EBF1/PDGFRB protein fusion with functional domains.
Description The fusion consists of the in-frame fusion of the N-terminal part of the transcription factor EBF1, including the DNA-binding domain, with the tyrosine kinase domain of PDGFRB.
Oncogenesis The tyrosine kinase domain of the fusion protein is constitutively activated, triggering downstream signalling.


The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW.
Blood. 2016 May 19;127(20):2391-405. doi: 10.1182/blood-2016-03-643544.
PMID 27069254
A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study.
Den Boer ML, van Slegtenhorst M, De Menezes RX, Cheok MH, Buijs-Gladdines JG, Peters ST, Van Zutven LJ, Beverloo HB, Van der Spek PJ, Escherich G, Horstmann MA, Janka-Schaub GE, Kamps WA, Evans WE, Pieters R.
Lancet Oncol. 2009 Feb;10(2):125-34. doi: 10.1016/S1470-2045(08)70339-5.
PMID 19138562
Successful tyrosine kinase inhibitor therapy in a refractory B-cell precursor acute lymphoblastic leukemia with EBF1-PDGFRB fusion.
Lengline E, Beldjord K, Dombret H, Soulier J, Boissel N, Clappier E.
Haematologica. 2013 Nov;98(11):e146-8.
PMID 24186319
Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia.
Roberts KG, Morin RD, Zhang J, Hirst M, Zhao Y, Su X, Chen SC, Payne-Turner D, Churchman ML, Harvey RC, Chen X, Kasap C, Yan C, Becksfort J, Finney RP, Teachey DT, Maude SL, Tse K, Moore R, Jones S, Mungall K, Birol I, Edmonson MN, Hu Y, Buetow KE, Chen IM, Carroll WL, Wei L, Ma J, Kleppe M, Levine RL, Garcia-Manero G, Larsen E, Shah NP, Devidas M, Reaman G, Smith M, Paugh SW, Evans WE, Grupp SA, Jeha S, Pui CH, Gerhard DS, Downing JR, Willman CL, Loh M, Hunger SP, Marra MA, Mullighan CG.
Cancer Cell. 2012 Aug 14;22(2):153-66. doi: 10.1016/j.ccr.2012.06.005.
PMID 22897847
Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia.
Roberts KG1, Li Y, Payne-Turner D, Harvey RC, Yang YL, Pei D, McCastlain K, Ding L, Lu C, Song G, Ma J, Becksfort J, Rusch M, Chen SC, Easton J, Cheng J, Boggs K, Santiago-Morales N, Iacobucci I, Fulton RS, Wen J, Valentine M, Cheng C, Paugh SW, Devidas M, Chen IM, Reshmi S, Smith A, Hedlund E, Gupta P, Nagahawatte P, Wu G, Chen X, Yergeau D, Vadodaria B, Mulder H, Winick NJ, Larsen EC, Carroll WL, Heerema NA, Carroll AJ, Grayson G, Tasian SK, Moore AS, Keller F, Frei-Jones M, Whitlock JA, Raetz EA, White DL, Hughes TP, Guidry Auvil JM, Smith MA, Marcucci G, Bloomfield CD, Mrózek K, Kohlschmidt J, Stock W, Kornblau SM, Konopleva M, Paietta E, Pui CH, Jeha S, Relling MV, Evans WE, Gerhard DS, Gastier-Foster JM, Mardis E, Wilson RK, Loh ML, Downing JR, Hunger SP, Willman CL, Zhang J, Mullighan CG.
N Engl J Med. 2014 Sep 11;371(11):1005-15. doi: 10.1056/NEJMoa1403088.
PMID 25207766
EBF1-PDGFRB fusion in paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL): genetic profile and clinical implications
Schwab C, Ryan SL, Chilton L, Elliott A, Murray J, Richardson S, Wragg C, Moppett J, Cummins M, Tunstall O, Parker CA, Saha V, Goulden N, Vora A, Moorman AV, Harrison CJ.
Blood, 2016 May 5;127(18):2214-8. doi: 10.1182/blood-2015-09-670166.
PMID 26872634
Tyrosine kinase inhibitor therapy induces remission in a patient with refractory EBF1-PDGFRB positive acute lymphoblastic leukemia.
Weston BW, Hayden MA, Roberts KG, Bowyer S, Hsu J, Fedoriw G, Rao KW, Mullighan CG.
J Clin Oncol. 2013 Sep 1;31(25):e413-6.
PMID 23835704


This paper should be referenced as such :
Gauthier Decool, Benoit Ducourneau, Nicolas Duployez, Catherine Roche-Lestienne
del(5)(q32q33) EBF1/PDGFRB
Atlas Genet Cytogenet Oncol Haematol. 2017;21(8):300-302.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 del(5)(q32q33) EBF1/PDGFRB

External links

Mitelman databasedel(5)(q32q33)
arrayMap (UZH-SIB Zurich)Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Oct 8 16:35:14 CEST 2021

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us