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t(11;19)(q23;p13) KMT2A/MYO1F

Written2018-04Jean-Loup Huret
jean-loup.huret@atlasgeneticsoncology.org

Abstract Review on t(11;19)(q23;p13), with data on clinics, and the genes involved.

Keywords Chromosome 11; Chromosome 19; KMT2A; MYO1F; Acute myeloid leukemia

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424
ICD-Morpho 9891/3 Acute monoblastic and monocytic leukaemia
Atlas_Id 1406

Clinics and Pathology

Disease Acute myeloid leukemia
Phenotype / cell stem origin Seven cases are available, six of them were infant patients. Two were diagnosed with acute monocytic leukemia (AMoL) (Taki et al., 2005; Duhoux et al., 2011). There were also 4 other cases of infant AML, not otherwise specified (NOS) (Lo Nigro et al., 2002; Meyer et al. 2013) and 1 pediatric AML-NOS (Meyer et al. 2013).
Epidemiology In the large study by Meyer et al., 2013, the four cases (3 infant AML, 1 pediatric AML) were part of a series of 692 infant ALL, 160 infant AMLs, 339 pediatric AMLs, 313 pediatric ALLs, 415 adult ALLs and 373 adult AMLs. This chromosome abnormality seems so far restricted to a subset of patients: extremely young patients with a diagnosis of AML.
Clinics One patient was diagnosed at birth (Duhoux et al., 2011), and another one at 2 months of age (Taki et al., 2005).
Prognosis Scarce data: one patient died 5 days after admission (Taki et al., 2005).

Cytogenetics

Cytogenetics Morphological The t(11;19)(q23;p13.3) was the sole abnormality in the case described by Duhoux et al., 2011, while the cases of Lo Nigro et al., 2002 and Taki et al., 2005 were complex translocations.

Genes involved and Proteins

Gene NameKMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location 11q23.3
Dna / Rna 37 exons, spanning about 120 kb; 13-15 mRNA
Protein 3969 amino acids, 431 kDa; 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 NameMYO1F
Location 19p13.2
Dna / Rna 28 exons, 3297 nucleotides
Protein 1,098 amino acids; 124 KDa; Myosins are a large family of ATP-driven mechanoenzymes. MYO1F belong to myosin class I, which includes myosins that are able to interact with actin filaments and lipid membranes. Presence of three tail homology regions (TH1, TH2 and a SH3 domain named TH3). These "long-tailed" myosins (i.e. with additional TH2 and TH3) are able to crosslink actin filaments via the TH2 domain and generate mechanical activities using the actin cytoskeleton as a tract. MYO1F contains a myosin motor domain (amino acids 17 - 690); this motor domain contains an actin binding site. It has an ATPase activity/cycle with association/dissociation of myosin with actin. The motor domain is followed by an IQ domain (isoleucine/glutamine motifs, aa 693 - 722), and a TH1 domain (Tail Homology domain, aa 728 - 917). TheTH1 domain is responsible for membrane interaction and, within TH1, a pleckstrin homology PH domain which is a negatively charged phospholipids -binding motif. There are several phosphosites located in the TH2 domain, required for binding to microtubules and microfilaments. TH2 is alanine and proline-rich (aa 941 - 1000). The C-terminus is a SH3 domain (SRC Homology 3 domain, aa 1041 - 1098); it should mediate assembly of specific protein complexes via binding to proline-rich peptides. TLR4 activation induces phosphorylation of MYO1F. MYO1F is a cytosolic protein predominantly expressed in the immune system (Wenzel et al., 2015; Walklate et al., 2016).

Result of the chromosomal anomaly

Hybrid gene
Description KMT2A exon 9 was fused to MYO1F exon 2; the breakpoint was thus located within MLL intron 9 in the cases reported by Taki et al., 2005 and Duhoux et al., 2011. The breakpoint in KMT2A was in intron 10 in cases studied by Meyer et al. 2013.
  
Fusion Protein
 
  KMT2A_MYO1F fusion protein, with AT hooks, zinc fingers CXXC type from KMT2A in N-terminus, fused to the entire MYO1F protein in C-terminus.
  

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

The t(11;19)(q23;p13) fusing MLL with MYO1F is recurrent in infant acute myeloid leukemias
Duhoux FP, Ameye G, Libouton JM, Bahloula K, Iossifidis S, Chantrain CF, Demoulin JB, Poirel HA
Leuk Res 2011 Sep;35(9):e171-2
PMID 21620472
 
Two new partner genes of MLL and additional heterogeneity in t(11;19)(q23;p13) translocations
L. Lo Nigro, D.J. Slater, E.F. Rappaport, A. Biondi, S. Maude, M.D. Megonigal, et al.
Blood, 100 (2002), p. 531a
 
The MLL recombinome of acute leukemias in 2013
Meyer C, Hofmann J, Burmeister T, Groger D, Park TS, Emerenciano M, Pombo de Oliveira M, Renneville A, Villarese P, Macintyre E, Cave H, Clappier E, Mass-Malo K, Zuna J, Trka J, De Braekeleer E, De Braekeleer M, Oh SH, Tsaur G, Fechina L, van der Velden VH, van Dongen JJ, Delabesse E, Binato R, Silva ML, Kustanovich A, Aleinikova O, Harris MH, Lund-Aho T, Juvonen V, Heidenreich O, Vormoor J, Choi WW, Jarosova M, Kolenova A, Bueno C, Menendez P, Wehner S, Eckert C, Talmant P, Tondeur S, Lippert E, Launay E, Henry C, Ballerini P, Lapillone H, Callanan MB, Cayuela JM, Herbaux C, Cazzaniga G, Kakadiya PM, Bohlander S, Ahlmann M, Choi JR, Gameiro P, Lee DS, Krauter J, Cornillet-Lefebvre P, Te Kronnie G, Schafer BW, Kubetzko S, Alonso CN, zur Stadt U, Sutton R, Venn NC, Izraeli S, Trakhtenbrot L, Madsen HO, Archer P, Hancock J, Cerveira N, Teixeira MR, Lo Nigro L, Moricke A, Stanulla M, Schrappe M, Sedek L, Szczepanski T, Zwaan CM, Coenen EA, van den Heuvel-Eibrink MM, Strehl S, Dworzak M, Panzer-Grumayer R, Dingermann T, Klingebiel T, Marschalek R
Leukemia 2013 Nov;27(11):2165-76
PMID 23628958
 
The MYO1F, unconventional myosin type 1F, gene is fused to MLL in infant acute monocytic leukemia with a complex translocation involving chromosomes 7, 11, 19 and 22
Taki T, Akiyama M, Saito S, Ono R, Taniwaki M, Kato Y, Yuza Y, Eto Y, Hayashi Y
Oncogene 2005 Aug 4;24(33):5191-7
PMID 15897884
 
Myosin isoforms and the mechanochemical cross-bridge cycle.
Walklate J, Ujfalusi Z, Geeves MA.
J Exp Biol. 2016 Jan;219(Pt 2):168-74. doi: 10.1242/jeb.124594. Review.
PMID 26792327
 
Class I myosin Myo1e regulates TLR4-triggered macrophage spreading, chemokine release, and antigen presentation via MHC class II.
Wenzel J, Ouderkirk JL, Krendel M, Lang R.
Eur J Immunol. 2015 Jan;45(1):225-37. doi: 10.1002/eji.201444698. Epub 2014 Nov 2.
PMID 25263281
 

Citation

This paper should be referenced as such :
Huret JL
t(11;19)(q23;p13) KMT2A/MYO1F;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/t1119q23p13ID1406.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;19)(q23;p13) KMT2A/MYO1F

External links

Mitelman databaset(11;19)(q23;p13) [Case List]    t(11;19)(q23;p13) [Transloc-MCList] KMT2A/MYO1F [Fusion-MCList]
arrayMap (UZH-SIB Zurich)Morph ( 9891/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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