| Entity | t(8;13)(p12;q12)/ANLL-NHL --> 5' FIM - 3' FGFR1 ; stem-cell myeloproliferative disorder associated with the 8p12 chromosomal translocations; fused to the catalytic domain of FGFR1 |
| Disease | stem-cell myeloproliferative disorder characterized by myeloid hyperplasia, T -cell lymphoblastic leukemia/lymphoma and peripheral blood eosinophilia, and it generally progresses to acute myeloid leukemia; specific to the 8p12 chromosomal region |
| Prognosis | very poor (median survival: 12 mths) |
| Cytogenetics | usually, t(8;13)(p12;q12) occurs as a single anomaly; duplication of the der(13) was found during disease progression, suggesting that the crucial event might lie on this derivative chromosome; additional abnormalities:+8, +21 |
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| Hybrid/Mutated Gene | 5' FIM - 3' FGFR1; localisation: der(13) |
| Abnormal Protein | aberrant tyrosine kinase composed of the N-term two-thirds of FIM (retaining the 10 putative zinc finger motifs), and the FGFR1 intracellular region minus the major part of the juxtamembrane domain |
| Oncogenesis | constitutive kinase activity of FGFR1 through constitutive activation of FGFR1 signal transduction pathways via constitutive dimerization capability mediated by the FIM N-term zinc finger sequences |
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| Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13). |
| Popovici C, Adˆ©laˆØde J, Ollendorff V, Chaffanet M, Guasch G, Jacrot M, Leroux D, Birnbaum D, Pˆ©busque MJ |
| Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (10) : 5712-5717. |
| PMID 9576949 |
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| The t(8;13)(p11;q11-12) rearrangement associated with an atypical myeloproliferative disorder fuses the fibroblast growth factor receptor 1 gene to a novel gene RAMP. |
| Smedley D, Hamoudi R, Clark J, Warren W, Abdul-Rauf M, Somers G, Venter D, Fagan K, Cooper C, Shipley J |
| Human molecular genetics. 1998 ; 7 (4) : 637-642. |
| PMID 9499416 |
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| FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome. |
| Xiao S, Nalabolu SR, Aster JC, Ma J, Abruzzo L, Jaffe ES, Stone R, Weissman SM, Hudson TJ, Fletcher JA |
| Nature genetics. 1998 ; 18 (1) : 84-87. |
| PMID 9425908 |
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| Characterization of FIM-FGFR1, the fusion product of the myeloproliferative disorder-associated t(8;13) translocation. |
| Ollendorff V, Guasch G, Isnardon D, Galindo R, Birnbaum D, Pˆ©busque MJ |
| The Journal of biological chemistry. 1999 ; 274 (38) : 26922-26930. |
| PMID 10480903 |
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| ZNF198-FGFR1 transforming activity depends on a novel proline-rich ZNF198 oligomerization domain. |
| Xiao S, McCarthy JG, Aster JC, Fletcher JA |
| Blood. 2000 ; 96 (2) : 699-704. |
| PMID 10887137 |
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