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

2018-04-01   Jean-Loup Huret 



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

Clinics and Pathology


Acute myeloid leukemia

Phenotype stem cell 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).


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.


One patient was diagnosed at birth (Duhoux et al., 2011), and another one at 2 months of age (Taki et al., 2005).


Scarce data: one patient died 5 days after admission (Taki et al., 2005).

Genes Involved and Proteins

Gene name
KMT2A (myeloid/lymphoid or mixed lineage leukemia)
Dna rna description
37 exons, spanning about 120 kb; 13-15 mRNA
Protein description
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 name
Dna rna description
28 exons, 3297 nucleotides
Protein description
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


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.
Atlas Image
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.


Pubmed IDLast YearTitleAuthors
216204722011The t(11;19)(q23;p13) fusing MLL with MYO1F is recurrent in infant acute myeloid leukemias.Duhoux FP et al
236289582013The MLL recombinome of acute leukemias in 2013.Meyer C et al
158978842005The 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 et al
267923272016Myosin isoforms and the mechanochemical cross-bridge cycle.Walklate J et al
252632812015Class I myosin Myo1e regulates TLR4-triggered macrophage spreading, chemokine release, and antigen presentation via MHC class II.Wenzel J et al


Fusion gene



Jean-Loup Huret

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

Atlas Genet Cytogenet Oncol Haematol. 2018-04-01

Online version: http://atlasgeneticsoncology.org/haematological/1406/t(11;19)(q23;p13)

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