t(5;11)(q33;q13) NUMA1/PDGFRB a novel fusion

2017-03-01   Emmanuelle Clappier , Ibrahima Ba , Virginie Eclache 

1.Hematology Laboratory, APHP, Hôpital Saint-Louis, Paris, France; Hematology Laboratory, APHP, Hôpital Avicenne, Bobigny, France; ibrahima.ba@aphp.fr; virginie.eclache@aphp.fr; emmanuelle.clappier@aphp.fr
2.Hematology Laboratory, APHP, Hôpital Saint-Louis, Paris, France; Hematology Laboratory, APHP, Hôpital Avicenne, Bobigny, France; ibrahima.ba@aphp.fr; virginie.eclache@aphp.fr; emmanuelle.clappier@aphp.fr
3.Hematology Laboratory, APHP, Hôpital Saint-Louis, Paris, France; Hematology Laboratory, APHP, Hôpital Avicenne, Bobigny, France; ibrahima.ba@aphp.fr; virginie.eclache@aphp.fr; emmanuelle.clappier@aphp.fr

Abstract

A novel NUMA1/PDGFRB fusion identified in B-cell precursor acute lymphoblastic leukemia is described.

Clinics and Pathology

Disease

B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Phenotype stem cell origin

Common-B immunophenotype (B-II EGIL classification): CD19+, CD22+, CD79a+, CD10+, Cμ -

Epidemiology

Only one case described, a 61-year-old man.

Treatment

GRAAL 2012 (Group for Research in Adult Acute Lymphoblastic Leukemia).

Cytogenetics

Cytogenetics morphological

Unbalanced t(5;11): t(5;11)(q33;q13),+der(5)t(5;11).
Atlas Image
CGH analysis suggested a rearrangement between 5q33 and 11q13.

Genes Involved and Proteins

Gene name
PDGFRB (platelet-derived growth factor receptor, beta polypeptide)
Location
5q32
Dna rna description
PDGFRB locus spans approximately 149.5 Mb and contains 23 exons. PDGFRB has been involved in over 30 gene fusion (Roberts, 2012; Kobayashi, 2014).
Protein description
The PDGRFB gene encodes a protein of 1106 amino acids with a molecular weight of approximately 124 kDa. Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Play an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD - leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB.
Gene name
NUMA1 (nuclear mitotic apparatus protein 1)
Location
11q13.4
Dna rna description
NUMA1 locus spans approximately 78 kb and contains 27 exons.; NUMA1 has been involved in a gene fusion with RARA (Wells RA, 1997; Melnick, 1999)
Protein description
The NUMA1 gene encodes a protein of 2115 amino acids with a molecular weight of approximately 230 kDa. Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume. Required for maintenance and establishment of the mitotic spindle poles, functioning as a tether linking bulk microtubules of the spindle to centrosomes. May be involved in coordination of the alignment of the mitotic spindle to the cellular polarity axis, which is a prerequisite for asymmetric cell divisions (Silk, 2009).

Result of the Chromosomal Anomaly

Atlas Image
The cDNA sequence analysis identified an in frame transcript fusing exon 22 of NUMA1 with exon 10 of PDGFRB

Description

5 NUTM1 - 3 PDGFRB. NUMA1 exon 22 is fused in frame with PDGFRB exon 11.

Transcript

The NUMA1-PDGFRB fusion transcript was amplified.
Atlas Image
NUTM1/PDGFRB fusion protein.

Highly cited references

Pubmed IDYearTitleCitations
284498102017Novel t(5;11)(q32;q13.4) with NUMA1-PDGFRB fusion in a myeloid neoplasm with eosinophilia with response to imatinib mesylate.1

Bibliography

Pubmed IDLast YearTitleAuthors
192552462009Requirements for NuMA in maintenance and establishment of mammalian spindle poles.Silk AD et al
246286262014ATF7IP as a novel PDGFRB fusion partner in acute lymphoblastic leukaemia in children.Kobayashi K et al
102338711999Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia.Melnick A et al
213303212011The kinase inhibitor TKI258 is active against the novel CUX1-FGFR1 fusion detected in a patient with T-lymphoblastic leukemia/lymphoma and t(7;8)(q22;p11).Wasag B et al
228978472012Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia.Roberts KG et al

Summary

Fusion gene

NUMA1/PDGFRB
Atlas Image
t(5;11)(q33;q13) R-banding, courtesy Virginie Eclache.

Citation

Emmanuelle Clappier ; Ibrahima Ba ; Virginie Eclache

t(5;11)(q33;q13) NUMA1/PDGFRB a novel fusion

Atlas Genet Cytogenet Oncol Haematol. 2017-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1693/t(5;11)(q33;q13)-numa1-pdgfrb-a-novel-fusion

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