t(4;22)(q12;q11) BCR/PDGFRA

2004-09-01   Barbara K Goodman , Anne Michele Safely 

1.Clinical Cytogenetics, Molecular Diagnostics Laboratories, Duke University Health System, Box 3631, Durham, NC 27710, UK

Clinics and Pathology


Reported in 3 cases; myeloproliferative disorder : atypical chronic myeloid leukemia (aCML) (Philadelphia chromosome-negative) .


One case was post-treatment for lymphoma, thus suspected to be a secondary MPD.


3 cases shared characteristics of splenic enlargement, eosinophilia and male predominance.
Atlas Image
Peripheral blood smear showing anemia, leukocytosis with increased granulocytes and precursors, and eosinophilia. Bone marrow showing hypercellularity with marked myeloid hyperplasia, mild eosinophilia, no increase in blasts.


One patient on treatment with good response to imatinib mesylate.



t(4;22)(q12;q11.2), easily distinguished cytogenetically.

Cytogenetics molecular

FISH for BCR- ABL1 is negative for fusion but will show extra signal for BCR when using the dual fusion probe set. BCR-ABL1 PCR is negative.
Atlas Image
Interphase FISH showing 3 signals for BCR (green), suggesting rearrangement. Two normal signals for ABL1 (red).

Additional anomalies

The t(4;22) was observed as the sole anomaly in the few reported cases to date.

Genes Involved and Proteins

Gene name
PDGFRA (platelet-derived growth factor receptor, alpha polypeptide)
Member of the protein-tyrosine kinase receptor family subclass III that includes the colony stimulating factor-1, c-KIT, FLT1, and FLT3/FLK2. Suggested role for normal PDGFRA receptor expression during periods of glial cell development and connective tissue growth.
Dna rna description
23 exons; includes 2 intracellular tyrosine kinase domains, TK1 and TK2 (exons 13-15 and 17-21), 5 extracellular Ig-like domains (exons 3-10), and a hydrophobic transmembrane domain (exon 10). The cytoplasmic region also encodes an ATP binding site.
Protein description
170-kD transmembrane glycoprotein that normally binds all PDGF isoforms, AA, AB, and BB at its extracellular Ig domain.
Gene name
BCR (Breakpoint cluster region)
Dna rna description
23 exons; alternate splicing.
Protein description
160-kDa protein; contains a unique serine/threonine kinase activity and at least two SH2 binding sites encoded in its first exon and a C-terminal domain that functions as a GTPase activating protein for p21(rac).

Result of the Chromosomal Anomaly


5BCR-3PDGFRA fusion


Fusion of BCR exon 7, 12 or 17 (in 3 cases described) with PDGFRA exon 12, in frame, containing intronic sequence from BCR in two cases.169 kDa protein in one case, somewhat smaller in two others.

Expression localisation

Predicted to be localized intracellularly


Alteration of tyrosine kinase activity secondary to loss of regulatory and PDGF binding domains; also, BCR domains may significantly affect BCR-PDGFRA downstream signaling pathways as seen with BCR-ABL fusion.


Pubmed IDLast YearTitleAuthors
120239812002The t(4;22)(q12;q11) in atypical chronic myeloid leukaemia fuses BCR to PDGFRA.Baxter EJ et al
125424822003Novel translocations that disrupt the platelet-derived growth factor receptor beta (PDGFRB) gene in BCR-ABL-negative chronic myeloproliferative disorders.Baxter EJ et al
123533192002CML after treatment for lymphoid malignancy: Therapy-related CML or coincidence?Bolaños-Meade J et al
25363721989Identification and structural analysis of the A type receptor for platelet-derived growth factor. Similarities with the B type receptor.Claesson-Welsh L et al
125222572003PDGFRA activating mutations in gastrointestinal stromal tumors.Heinrich MC et al
85864211995Structure, organization, and transcription units of the human alpha-platelet-derived growth factor receptor gene, PDGFRA.Kawagishi J et al
94070861997Functional importance of platelet-derived growth factor (PDGF) receptor extracellular immunoglobulin-like domains. Identification of PDGF binding site and neutralizing monoclonal antibodies.Lokker NA et al
107482922000A FISH study of variant Philadelphia rearrangements.Reddy KS et al
150348672004Molecular and cytogenetic characterization of a novel translocation t(4;22) involving the breakpoint cluster region and platelet-derived growth factor receptor-alpha genes in a patient with atypical chronic myeloid leukemia.Safley AM et al
129449192003Chronic myeloproliferative disorders with rearrangement of the platelet-derived growth factor alpha receptor: a new clinical target for STI571/Glivec.Trempat P et al


Fusion gene

BCR/PDGFRA BCR (22q11.23) PDGFRA (4q12) M t(4;22)(q12;q11)|BCR/PDGFRA BCR (22q11.23) PDGFRA (4q12) TIC
Atlas Image
Partial karyotype showing chromosomes 4 and 22.


Barbara K Goodman ; Anne Michele Safely

t(4;22)(q12;q11) BCR/PDGFRA

Atlas Genet Cytogenet Oncol Haematol. 2004-09-01

Online version: http://atlasgeneticsoncology.org/haematological/1153/t(4;22)(q12;q11)-bcr-pdgfra

External Links