| Written | 2002-04 | Mariko Eguchi |
| Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK |
| Identity |
| ICD-Topo | C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| ICD-Morpho | 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS |
| ICD-Morpho | 9920/3 Therapy-related myeloid neoplasms |
| Atlas_Id | 1198 |
 | |
| t(11;14)(q23;q24), G-banding | |
| Clinics and Pathology |
| Disease | AML and therapy related AL |
| Phenotype / cell stem origin | monoblastic, unclassified |
| Epidemiology | Rare. Three cases reported so far. |
| Prognosis | Very poor. Less than 2 months survival in two cases. |
| Cytogenetics |
| Additional anomalies | Not found in mainline in reported cases. |
| Genes involved and Proteins |
| Gene Name | KMT2A (myeloid/lymphoid or mixed lineage leukemia) |
| Location | 11q23.3 |
| Dna / Rna | 36 exons, spans over 100kb, ORF 12kb. |
| Protein | 3969 amino acids; 431 kDa; contains two DNA binding motifs (a AT hook and a DNA methyltransferase homology motif), trithorax homology domains, zinc finger domains with features of PHD fingers and the C-terminal SET domain. |
| Gene Name | GPHN (Gephyrin) |
| Location | 14q23.3 |
| Dna / Rna | 29 exons, spans approximately 800kb, ORF 2.3kb |
| Protein | 736 to 770 amino acids; 93-105 kDa; submembraneous scaffold protein that anchors glycine receptor to postsynaptic cytoskeletal elements through a putative microtubule binding motif. GPHN is also involved in molybdenum cofactor biosynthesis (MoaB, MogA and MoeA homology domain), and interacts with RAFT-1. |
| Result of the chromosomal anomaly |
| Description | 5' MLL-3' GPHN on der (11) |
| Transcript | no GPHN-MLL reciprocal transcript |
| MLL-GPHN protein | |
| Description | C-terminal half of GPHN, including the suspected putative microtubule binding motif and MoeA homology domain, is fused to the N-terminal portion of MLL. |
| 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 |
| Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins. |
| Ayton PM, Cleary ML |
| Oncogene. 2001 ; 20 (40) : 5695-5707. |
| PMID 11607819 |
| The human gephyrin (GPHN) gene: structure, chromosome localization and expression in non-neuronal cells. |
| David-Watine B |
| Gene. 2001 ; 271 (2) : 239-245. |
| PMID 11418245 |
| GPHN, a novel partner gene fused to MLL in a leukemia with t(11;14)(q23;q24). |
| Eguchi M, Eguchi-Ishimae M, Seto M, Morishita K, Suzuki K, Ueda R, Ueda K, Kamada N, Greaves M |
| Genes, chromosomes & cancer. 2001 ; 32 (3) : 212-221. |
| PMID 11579461 |
| Receptors, gephyrin and gephyrin-associated proteins: novel insights into the assembly of inhibitory postsynaptic membrane specializations. |
| Kneussel M, Betz H |
| The Journal of physiology. 2000 ; 525 Pt 1 : 1-9. |
| PMID 10811719 |
| t(11;14)(q23;q24) generates an MLL-human gephyrin fusion gene along with a de facto truncated MLL in acute monoblastic leukemia. |
| Kuwada N, Kimura F, Matsumura T, Yamashita T, Nakamura Y, Wakimoto N, Ikeda T, Sato K, Motoyoshi K |
| Cancer research. 2001 ; 61 (6) : 2665-2669. |
| PMID 11289145 |
| Leukemic evolution in three patients with myelodysplastic syndrome and unusual chromosome changes. |
| Palka G, Calabrese G, Stuppia L, Guanciali Franchi P, Antonucci A, Spadano A, Di Lorenzo R, Torlontano G |
| Cancer genetics and cytogenetics. 1992 ; 61 (2) : 162-164. |
| PMID 1638498 |
| Primary structure and alternative splice variants of gephyrin, a putative glycine receptor-tubulin linker protein. |
| Prior P, Schmitt B, Grenningloh G, Pribilla I, Multhaup G, Beyreuther K, Maulet Y, Werner P, Langosch D, Kirsch J |
| Neuron. 1992 ; 8 (6) : 1161-1170. |
| PMID 1319186 |
| Citation |
| This paper should be referenced as such : |
| Eguchi, M |
| t(11;14)(q23;q24) |
| Atlas Genet Cytogenet Oncol Haematol. 2002;6(3):213-214. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t1114q23q24ID1198.html |
| Other genes implicated (Data extracted from papers in the Atlas) [ 2 ] |
| Genes | GPHN | KMT2A |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(11;14)(q23;q24) KMT2A/GPHN | |
| 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 17:20:04 CEST 2017 |
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