| Written | 2004-01 | Jacques Boyer |
| Laboratoire d' hématologie, CH du MANS, France |
| Identity |
| ICD-Topo | C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| ICD-Morpho | 9967/3 Myeloid and lymphoid neoplasms with FGFR1 rearrangement |
| ICD-Morpho | 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable |
| Atlas_Id | 1129 |
| Note | 8p12 myeloproliferative syndrome (EMS) / stem cell leukemia-lymphoma syndrome (SCLL) belongs to the tyrosine kinase fusion genes chronic myeloproliferative diseases . It is associated with recurent translocations : |
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| t(8;9)(p12;q33) G- banding - Courtesy Melanie Zenger and Claudia Haferlach. | |
| Clinics and Pathology |
| Disease | Myeloproliferative disorder that is frequently associated with T-cell, or less commonly B-cell non Hodgkin lymphoma. |
| Phenotype / cell stem origin | May involve a stem cell. |
| Epidemiology | 9 cases are described ; sexe ratio : 6M/3F. |
| Clinics | Agressive disease ; myeloid hyperplasia progressing to myelodysplasia and T or B-cell lymphoma, splenomegaly, lymph node. High WBC with myelemia with frequently eosinophilia and sometimes monocytosis (near CMLL). |
| Evolution | The disease transforms to AML or occasionally ALL in a median of 6 months. |
| Prognosis | Median survival : 12 months. |
| Cytogenetics |
| Cytogenetics Morphological | This translocation is a variant of the t(8 ;13)(p12 ;q12). |
| Additional anomalies | +der(9), +21 |
| Genes involved and Proteins |
| Gene Name | FGFR1 (Fibroblast Growth Factor Receptor 1) |
| Location | 8p11.23 |
| Gene Name | CNTRL (centriolin) |
| Location | 9q33.2 |
| Dna / Rna | DNA : 26kb - 19 exons RNA : Three mains transcripts of approximatly 7.5, 4.5 and 1.5 kb. CEP transcripts are barely expressed in thymus and peripheral blood cells. |
| Protein | CEP110 gene codes for a 994-amino acid coiled-coil protein with 4 consensus leucine zippers (centrosome associated P110 protein). |
| Result of the chromosomal anomaly |
| Description | The t(8;9) breakpoint in the FGFR1 gene is localized in exon 8, 12 bp upstream of the exon 8/intron 8 junction. It is distinct from the breakpoints in the t(6;8) and t(8;13) but it preserves the same FGFR1 sequence in the chimeric protein. The breakpoint in the CEP110 is localized in exon 15. The translocation leads to the formation of the two reciprocal transcripts. |
| Description | |
| Oncogenesis | Activated aberrant tyrosine kinase are likely to promote leukemogenesis through contitutive activation of the FGFR1 kinase. This activation may be mediated by dimerisation of the portion of the fusion protein wich contains the leucine zippers. This activation may interacts with the cell proliferation and the apoptose, additional anomalies may also play an important role in the evolution of the disease. |
| 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. | |
| Case Report | Translocation t(8;9)(p12;q33) detected in cALL: A case report |
| Bibliography |
| Tyrosine kinase fusion genes in chronic myeloproliferative diseases. |
| Cross NC, Reiter A |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 ; 16 (7) : 1207-1212. |
| PMID 12094244 |
| FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33). |
| Guasch G, Mack GJ, Popovici C, Dastugue N, Birnbaum D, Rattner JB, Pébusque MJ |
| Blood. 2000 ; 95 (5) : 1788-1796. |
| PMID 10688839 |
| The 8p11 myeloproliferative syndrome: a distinct clinical entity caused by constitutive activation of FGFR1. |
| Macdonald D, Reiter A, Cross NC |
| Acta haematologica. 2002 ; 107 (2) : 101-107. |
| PMID 11919391 |
| R?éarrangements chromosomiques et syndromes my?éloprolif?é mixtes. |
| Popovici C |
| Thè Aix Marseille II,. 1998. |
| Identification of four new translocations involving FGFR1 in myeloid disorders. |
| Sohal J, Chase A, Mould S, Corcoran M, Oscier D, Iqbal S, Parker S, Welborn J, Harris RI, Martinelli G, Montefusco V, Sinclair P, Wilkins BS, van den Berg H, Vanstraelen D, Goldman JM, Cross NC |
| Genes, chromosomes & cancer. 2001 ; 32 (2) : 155-163. |
| PMID 11550283 |
| Citation |
| This paper should be referenced as such : |
| Boyer, J |
| t(8;9)(p12;q33) |
| Atlas Genet Cytogenet Oncol Haematol. 2004;8(2):92-93. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t0809p12q33ID1129.html |
| Other genes implicated (Data extracted from papers in the Atlas) [ 1 ] |
| Genes | FGFR1 |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(8;9)(p12;q33) CNTRL/FGFR1 | |
| 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 : Mon Sep 18 17:19:47 CEST 2017 |
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