t(11;15)(q23;q14) KMT2A/ZFYVE19

2015-01-01   Jean-Loup Huret 

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

Clinics and Pathology

Disease

Acute myeloid leukemia (AML).

Epidemiology

Only one case to date, a 11-year-old boy with de novo acute myeloblastic leukemia (AML-M2) (Chinwalla et al., 2003).

Note

ZFYVE19 is located 170kb telomeric to CASC5.on chromosome 15. Two in-frame fusions were detected in this patient, in which 5 MLL was fused both to ZFYVE19 and CASC5. Fusion junctions were : .... PKTTPSEPKKKQPPP from MLL (amino acid 1334), fused to PQNYKKRVAALEAKQK.... from ZFYVE19 (amino acid 146), and .... APRPSIPVKQKPKEK from MLL, fused to IFDHHTEEDIDKSAN.... from CASC5.

Genes Involved and Proteins

Gene name
KMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location
11q23.3
Note
KMT2A (HGNC official name!) is better known as MLL.
Protein description
3969 amino acids; Transcriptional regulatory factor. MLL is known to be associated with more than 30 proteins, including the core components of the SWI/SNF chromatin remodeling complex and the transcription complex TFIID. MLL binds promotors of HOX genes through acetylation and methylation of histones. MLL is a major regulator of hematopoesis and embryonic development, through regulation of HOX genes expression regulation (HOXA9 in particular). , Cytokinesis is the final stage of cell division.There is an abscission checkpoint (also termed "NoCut") which depends on AURKB (17p13.1). The membrane abscission is mediated by the ESCRT machinery through the activity of the VPS4 proteins (VPS4A, 16q22.1 and VPS4B, 18q21.33). VPS4 localizes transiently to the midbody ring towards the end of cytokinesis. ZFYVE19 and CHMP4C (8q21.13) bind VPS4 following checkpoint, and AURKB sustains this ternary complex. Termination of AURKB-mediated signalling results in dephosphorylation of CHMP4C, followed by dislocation of the ternary complex, and release of VPS4, which is then activated to complete abscission (Thoresen et al., 2014).
Gene name
ZFYVE19 (zinc finger FYVE-type containing 19)
Location
15q15.1
Note
ZFYVE19 is also known as ANCHR (for Abscission/NoCut Checkpoint Regulator), or MPFYVE (for MLL Partner Containing FYVE Domain).
Protein description
471 amino acids. ZFYVE19 contains a Zinc finger FYVE-type (amino acids 74-133), MIM1 domains (type-1 microtubule interacting and transport (MIT) domain-interacting motifs MIMs, to mediate interaction between ESCRT-III proteins and the VPS4 MIT domain): MIM1-A (aa 174-187) and MIM1-B (aa 326-339), and a B-box domain in C-term.

Result of the Chromosomal Anomaly

Description

Exon 7 of MLL was fused to exon 3 of ZFYVE19.
Atlas Image

Description

The MLL/ZFYVE19 fusion protein is a 1435 amino acids protein with a molecular mass of 160 kDa. It contains the AT-hooks and the repression domain of MLL and the C-term of ZFYVE19, without the N-term Zinc finger FYVE-type domain of ZFYVE19.

Bibliography

Pubmed IDLast YearTitleAuthors
126187662003A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15.Chinwalla V et al
248145152014ANCHR mediates Aurora-B-dependent abscission checkpoint control through retention of VPS4.Thoresen SB et al

Summary

Fusion gene

KMT2A/ZFYVE19 KMT2A (11q23.3) ZFYVE19 (15q15.1) COF 1872 1873|KMT2A/ZFYVE19 KMT2A (11q23.3) ZFYVE19 (15q15.1) TIC

Citation

Jean-Loup Huret

t(11;15)(q23;q14) KMT2A/ZFYVE19

Atlas Genet Cytogenet Oncol Haematol. 2015-01-01

Online version: http://atlasgeneticsoncology.org/haematological/1421/t(11;15)(q23;q14)

External Links