t(11;19)(q23;p13) KMT2A/SH3GL1

2014-11-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

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 description
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 description
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 2.1564 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).

Bibliography

Pubmed IDLast YearTitleAuthors
247044502014EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion.Huang EW et al
227955372012De novo mutations in MLL cause Wiedemann-Steiner syndrome.Jones WD et al
150771842004Functional contribution of EEN to leukemogenic transformation by MLL-EEN fusion protein.Liu H et al
91222351997EEN 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 et al

Summary

Fusion gene

KMT2A/SH3GL1 KMT2A (11q23.3) SH3GL1 (19p13.3) COF 1914 1915|KMT2A/SH3GL1 KMT2A (11q23.3) SH3GL1 (19p13.3) TIC

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.

Citation

Jean-Loup Huret

t(11;19)(q23;p13) KMT2A/SH3GL1

Atlas Genet Cytogenet Oncol Haematol. 2014-11-01

Online version: http://atlasgeneticsoncology.org/haematological/1194/t(11;19)(q23;p13)

External Links