MLLT10 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10)

2005-10-01   Cristina Morerio , Claudio Panarello 

Dipartimento di Ematologia ed Oncologia Pediatrica, IRCCS Istituto Giannina Gaslini, Largo G. Gaslini 5, 16147 Genoa, Italy

Identity

HGNC
LOCATION
10p12.31
IMAGE
Atlas Image
LEGEND
AF10 (10p12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
FUSION GENES

DNA/RNA

Transcription

5 telomeric --> 3 centromeric direction; 5.5 kb mRNA; coding sequence: 3.1 kb

Proteins

Atlas Image
Representation of the AF10 protein modified by Linder B et al. J Mol Biol 2000 and Jones LK et al. Leukemia 2001.

Description

1027 amino acids; 109 KDa; N-term - LAP (leukemia associated protein)/PHD finger - Ext-LAP/PHD (Cys-rich region) - NLS (nuclear localisation signal) - AT-hook - LZ (leucine zipper) - Gln-rich domain - C-term

Expression

mainly in the testis

Localisation

nuclear

Function

transcription factor

Homology

with AF17 and BR140

Implicated in

Entity name
Disease
mainly M4/M5 AML
Cytogenetics
Due to the opposite orientation of AF10 and MLL on their respective chromosome arms, MLL-AF10 gene fusion requires complex rearrangements with three or more breakpoints. An inversion of the 5MLL or 3AF10 is required in order to allow an in-frame MLL-AF10 fusion.
Hybrid gene
5 MLL - 3 AF10; breakpoints are at variable places along AF10
Fusion protein
The AF10 Ext-LAP/PHD is always deleted, as are the MLL PHD fingers. Both retain the C-term LZ domain necessary for malignant transformation.
Entity name
inv ins(10;11)(p12;q23q12)/AML -->KMT2A - MLLT10
Disease
One case of pediatric M5 AML
Hybrid gene
5 MLL - 3 AF10 and 5 AF10 - 3 HEAB, a gene at 11q12
Fusion protein
only MLL-AF10 is expressed
Entity name
t(10;11)(p13;q14-21)-->CALM-MLLT10 and/or AF10-CALM
Disease
Present both in myeloid and non myeloid acute leukemias: in T-cell ALL specific to TCRgd lineage; in myeloid leukemia described in FAB M0-AML, M1-AML, M5-AML, M7-AML.
Prognosis
poor
Cytogenetics
may well be confused with the above t(10;11)(p12;q23)
Hybrid gene
5 CALM - 3 AF10 and 5 AF10 - 3 CALM
In a 5 breakpoint cluster region (nucleotides 424 and 589), AF10 sequences retained the Ext-LAP/PHD domain. The presence of these kind of sequences seems to be necessary for maturation toward the TCRgd lineage, whereas their absence leads to maturation arrest at a more immature stage.
Fusion protein
both CALM-AF10 and the reciprocal AF10-CALM are expressed. However, the CALM-AF10 contains most of the functional domains present in each of the two proteins.

Breakpoints

Atlas Image

Note

the breakpoint in the t(10;11)(p13;q14-21) is more in 5 of AF10

Bibliography

Pubmed IDLast YearTitleAuthors
126767842003CALM-AF10 is a common fusion transcript in T-ALL and is specific to the TCRgammadelta lineage.Asnafi V et al
75429101995Molecular basis of 11q23 rearrangements in hematopoietic malignant proliferations.Bernard OA et al
106374822000Molecular analysis of the CALM/AF10 fusion: identical rearrangements in acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma patients.Bohlander SK et al
76629541995The t(10;11) translocation in acute myeloid leukemia (M5) consistently fuses the leucine zipper motif of AF10 onto the HRX gene.Chaplin T et al
111354342001Molecular analysis of the genomic inversion and insertion of AF10 into MLL suggests a single-step event.Chaplin T et al
119862362002The AF10 leucine zipper is required for leukemic transformation of myeloid progenitors by MLL-AF10.DiMartino JF et al
96161631998MLL and CALM are fused to AF10 in morphologically distinct subsets of acute leukemia with translocation t(10;11): both rearrangements are associated with a poor prognosis.Dreyling MH et al
114174762001Identification and molecular characterisation of a CALM-AF10 fusion in acute megakaryoblastic leukaemia.Jones LK et al
93658321997Hematologic malignancies with the t(10;11) (p13;q21) have the same molecular event and a variety of morphologic or immunologic phenotypes.Kobayashi H et al
95932841998The t(10;11)(p12;q23) translocation in acute leukaemia: a cytogenetic and clinical study of 20 patients. European 11q23 Workshop participants.Lillington DM et al
98787871998Expression pattern and cellular distribution of the murine homologue of AF10.Linder B et al
108607452000Biochemical analyses of the AF10 protein: the extended LAP/PHD-finger mediates oligomerisation.Linder B et al
161115392005MLL-MLLT10 fusion gene in pediatric acute megakaryoblastic leukemia.Morerio C et al
8558942199611q23 rearrangements in acute leukemia.Rubnitz JE et al
118965372002Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia.Van Limbergen H et al
89770381996Chromosome abnormalities in leukaemia: the 11q23 paradigm.Young BD et al

Other Information

Locus ID:

NCBI: 8028
MIM: 602409
HGNC: 16063
Ensembl: ENSG00000078403

Variants:

dbSNP: 8028
ClinVar: 8028
TCGA: ENSG00000078403
COSMIC: MLLT10

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000078403ENST00000307729P55197
ENSG00000078403ENST00000377059P55197
ENSG00000078403ENST00000377072P55197
ENSG00000078403ENST00000377091P55197
ENSG00000078403ENST00000377100P55197
ENSG00000078403ENST00000420525H0Y5P4
ENSG00000078403ENST00000430455H0Y5C4
ENSG00000078403ENST00000438473Q5JT35
ENSG00000078403ENST00000462999A0A494C093
ENSG00000078403ENST00000495130A0A494C1P9
ENSG00000078403ENST00000621220P55197
ENSG00000078403ENST00000631589P55197
ENSG00000078403ENST00000650772A0A494C0R2
ENSG00000078403ENST00000650893A0A494C1P9
ENSG00000078403ENST00000651097A0A494C038
ENSG00000078403ENST00000651298A0A494C1P9
ENSG00000078403ENST00000652497P55197

Expression (GTEx)

0
10
20
30
40
50
60

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
124534192002ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation.256
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
254649002014AF10 regulates progressive H3K79 methylation and HOX gene expression in diverse AML subtypes.56
264809202016Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat.30
264393022015The PZP Domain of AF10 Senses Unmodified H3K27 to Regulate DOT1L-Mediated Methylation of H3K79.25
194436582009Global reduction of the epigenetic H3K79 methylation mark and increased chromosomal instability in CALM-AF10-positive leukemias.23
218045472011Common variation at 10p12.31 near MLLT10 influences meningioma risk.21
236738602013New MLLT10 gene recombinations in pediatric T-acute lymphoblastic leukemia.15
220643522012CALM/AF10-positive leukemias show upregulation of genes involved in chromatin assembly and DNA repair processes and of genes adjacent to the breakpoint at 10p12.14
180379642008The leukemogenic CALM/AF10 fusion protein alters the subcellular localization of the lymphoid regulator Ikaros.13

Citation

Cristina Morerio ; Claudio Panarello

MLLT10 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10)

Atlas Genet Cytogenet Oncol Haematol. 2005-10-01

Online version: http://atlasgeneticsoncology.org/gene/4/mllt10

Historical Card

1997-12-01 MLLT10 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10) by  Jean-Loup Huret 

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