Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

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

Written2015-01Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

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 1421

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).

Genetics

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.

Cytogenetics

Cytogenetics Morphological Complex karyotype.

Genes involved and Proteins

Gene NameKMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location 11q23.3
Note KMT2A (HGNC official name!) is better known as MLL.
Protein 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).
Gene NameZFYVE19 (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 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. 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).

Result of the chromosomal anomaly

Hybrid gene
Description Exon 7 of MLL was fused to exon 3 of ZFYVE19.
  
Fusion Protein
 
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.
  

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

A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15.
Chinwalla V, Chien A, Odero M, Neilly MB, Zeleznik-Le NJ, Rowley JD.
Oncogene. 2003 Mar 6;22(9):1400-10.
PMID 12618766
 
ANCHR mediates Aurora-B-dependent abscission checkpoint control through retention of VPS4.
Thoresen SB, Campsteijn C, Vietri M, Schink KO, Liestol K, Andersen JS, Raiborg C, Stenmark H.
Nat Cell Biol. 2014 Jun;16(6):550-60. doi: 10.1038/ncb2959. Epub 2014 May 11.
PMID 24814515
 

Citation

This paper should be referenced as such :
Jean-Loup Huret
t(11;15)(q23;q14) KMT2A/ZFYVE19
Atlas Genet Cytogenet Oncol Haematol. 2016;20(2):94-95.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t1115q23q14ID1421.html


Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

Genes KMT2A

Translocations implicated (Data extracted from papers in the Atlas)

 t(11;15)(q23;q14) KMT2A/ZFYVE19

External links

KMT2A (11q23.3) ZFYVE19 (15q15.1)

KMT2A (11q23.3) ZFYVE19 (15q15.1)

Mitelman databaset(11;15)(q23;q14) [Case List]    t(11;15)(q23;q14) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9807/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9813/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
COSMIC_fusionKMT2A/ZFYVE19 KMT2A (11q23.3) ZFYVE19 (15q15.1)   [fusion1872]   [fusion1873]  
TICdbKMT2A/ZFYVE19  KMT2A (11q23.3) ZFYVE19 (15q15.1)
 
Disease databaset(11;15)(q23;q14) KMT2A/ZFYVE19
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Sep 18 17:20:05 CEST 2017


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.