| Written | 2017-03 | Ibrahima Ba, Virginie Eclache, Emmanuelle Clappier |
| 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. |
| Keywords | Chromosome 5; chromosome 11; acute lymphoblastic leukemia; B-ALL; NUMA1; PDGFRB; translocation t(5;11)(q33;q13); fusion gene |
| Identity |
| ICD-Topo | C420,C421,C424 |
| ICD-Morpho | 9820/3 |
| Atlas_Id | 1693 |
 | |
| t(5;11)(q33;q13) R-banding, courtesy Virginie Eclache. | |
| Clinics and Pathology |
| Disease | B-cell precursor acute lymphoblastic leukemia (BCP-ALL). |
| Phenotype / cell stem 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). |
 | |
| 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 | 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 | 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 | 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 | 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 |
| 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. |
 | |
| NUTM1/PDGFRB fusion protein. | |
| 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. |
| Bibliography |
| Requirements for NuMA in maintenance and establishment of mammalian spindle poles |
| Alain D. Silk, Andrew J. Holland and Don W. Cleveland |
| J Cell Biol. 2009 ; 184(5): 677-690 |
| PMID 19255246 |
| ATF7IP as a novel PDGFRB fusion partner in acute lymphoblastic leukaemia in children |
| Kobayashi K, Mitsui K & Ohara A |
| Br J Haematol. 2014 ; 165(6):836-41 |
| PMID 24628626 |
| Deconstructing a Disease: RARA, Its Fusion Partners, and Their Roles in the Pathogenesis of Acute Promyelocytic Leukemia |
| Melnick A & Licht JD |
| Blood 1999 ; 93(10):3167-215 |
| PMID 10233871 |
| Fusion of retinoic acid receptor ? to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia |
| Richard A. Wells, Charles Catzavelos & Suzanne Kamel-Reid |
| Nature Genetics 1997 ; 17(1):109-13 |
| PMID 21330321 |
| Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia |
| Roberts KG, Morin RD & Mullighan CG |
| Cancer Cell 2012 ; 14;22(2):153-66 |
| PMID 22897847 |
| Citation |
| This paper should be referenced as such : |
| Ba I, Eclache V, Clappier E |
| t(5;11)(q33;q13) NUMA1/PDGFRB a novel fusion; |
| Atlas Genet Cytogenet Oncol Haematol. in press |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t0511q33q13ID1693.html |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(5;11)(q33;q13) NUMA1/PDGFRB | |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| All articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Tue Aug 28 18:17:10 CEST 2018 |
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