| Written | 2014-11 | Jean-Loup Huret |
| Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France |
| Identity |
| ICD-Topo | C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| ICD-Morpho | 9807/3 Mixed phenotype acute leukaemia with t(v;11q23); MLL rearranged |
| ICD-Morpho | 9813/3 B lymphoblastic leukaemia/lymphoma with t(v;11q23); MLL rearranged |
| ICD-Morpho | 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS |
| Atlas_Id | 1194 |
| Note | At least three other translocation t(11;19) involve KMT2A: the t(11;19)(q23;p13.1) KMT2A/ELL, the t(11;19)(q23;p13.3) KMT2A/MLLT1, and the t(11;19)(q23;p13.3) KMT2A/ACER1. |
| Clinics and Pathology |
| Epidemiology | Only one case to date, a 22-month-old girl with a diagnosis of acute myeloid leukemia not otherwise specified (So et al., 1997). |
| Genes involved and Proteins |
| Gene Name | KMT2A (myeloid/lymphoid or mixed lineage leukemia) |
| Location | 11q23.3 |
| Protein | KMT2A is better known as MLL. MLL is a transcriptional regulatory factor. MLL regulates chromatin-mediated transcription. MLL is a major regulator of hematopoesis and embryonic development, through regulation of HOX genes expression. Translocations involving MLL are associated with high-risk de novo or treatment-related acute myeloid leukemias and myelodysplastic syndromes and acute lymphoblastic leukemias (review in Huret, 2006). Mutations in MLL cause Wiedemann-Steiner syndrome (Jones et al., 2012). |
| Gene Name | SH3GL1 (extra eleven nineteen leukemia fusion gene) |
| Location | 19p13.3 |
| Note | The gene has previously been named EEN. |
| Protein | The protein, named endophilin-A2, is made of 368 amino acids (aa) in isoform 1. From N-term to C-term, it contains a Bin/Amphiphysin/Rvs (BAR) domain (aa 18-249), involved in curvature of the cell membrane, a coiled-coil domain (protein-protein interactions, aa 119-227), and a SH3 domain (protein-protein interactions, aa 306-365). Endophilin-A2 is involved in clathrin-mediated endocytosis. Endophilin-A2 facilitates G1/S cell cycle transition of multiple myeloma cells (Huang et al., 2014). |
| Result of the chromosomal anomaly |
| Description | 5' KMT2A - 3' SH3GL1. KMT2A exon 6 was fused to SH3GL1 exon 2. |
| Description | 1564 amino acids (1212 from KMT2A, and 352 from SH3GL1). The fusion protein retains the AT hooks (DNA binding) and the Zinc finger CXXC-type from KMT2A fused to most of SH3GL1, including the BAR domain and the SH3 domain. |
| Oncogenesis | KMT2A/SH3GL1 is localized in the nucleus, while SH3GL1 is located in the cytoplasm. KMT2A/SH3GL1 may drive to aberrant transcriptional regulation. KMT2A/SH3GL1 increases HOXA7 promoter activity (Liu et al., 2004). |
| 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 |
| EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion. |
| Huang EW, Xue SJ, Li XY, Xu SW, Cheng JD, Zheng JX, Shi H, Lv GL, Li ZG, Li Y, Liu CH, Chen XH, Liu H, Li J, Liu C. |
| Biochem Biophys Res Commun. 2014 May 2;447(2):271-7. |
| PMID 24704450 |
| MLL (myeloid/lymphoid or mixed lineage leukemia). |
| Huret JL. |
| Atlas Genet Cytogenet Oncol Haematol. 2006;10(2):83-87. http://atlasgeneticsoncology.org/Genes/MLLID13.html. |
| De novo mutations in MLL cause Wiedemann-Steiner syndrome. |
| Jones WD, Dafou D, McEntagart M, Woollard WJ, Elmslie FV, Holder-Espinasse M, Irving M, Saggar AK, Smithson S, Trembath RC, Deshpande C, Simpson MA. |
| Am J Hum Genet. 2012 Aug 10;91(2):358-64. |
| PMID 22795537 |
| Functional contribution of EEN to leukemogenic transformation by MLL-EEN fusion protein. |
| Liu H, Chen B, Xiong H, Huang QH, Zhang QH, Wang ZG, Li BL, Chen Z, Chen SJ. |
| Oncogene. 2004 Apr 22;23(19):3385-94. |
| PMID 15077184 |
| EEN encodes for a member of a new family of proteins containing an Src homology 3 domain and is the third gene located on chromosome 19p13 that fuses to MLL in human leukemia. |
| So CW, Caldas C, Liu MM, Chen SJ, Huang QH, Gu LJ, Sham MH, Wiedemann LM, Chan LC. |
| Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2563-8. |
| PMID 9122235 |
| Citation |
| This paper should be referenced as such : |
| Jean-Loup Huret |
| t(11;19)(q23;p13) KMT2A/SH3GL1 |
| Atlas Genet Cytogenet Oncol Haematol. 2015;19(9):194-195. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t1119q23p13ID1194.html |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(11;19)(q23;p13) KMT2A/SH3GL1 | |
| 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 Jul 8 15:28:09 CEST 2019 |
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