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


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)
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)
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


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.


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).


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


Fusion gene

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


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.


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)