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

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

Written	1997-12	Jean-Loup Huret
		Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated	2005-10	Cristina Morerio, Claudio Panarello
		Dipartimento di Ematologia ed Oncologia Pediatrica, IRCCS Istituto Giannina Gaslini, Largo G. Gaslini 5, 16147 Genoa, Italy

(Note : for Links provided by Atlas : click)

Identity

Alias_names	myeloid/lymphoid or mixed-lineage leukemia (trithorax (Drosophila) homolog); translocated to, 10
	myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10
Alias_symbol (synonym)	AF10
Other alias	AF10 (ALL1 fused gene from chromosome 10)
HGNC (Hugo)	MLLT10
LocusID (NCBI)	8028
Atlas_Id	4
Location	10p12.31 [Link to chromosome band 10p12]
Location_base_pair	Starts at 21534645 and ends at 21743630 bp from pter ( according to hg19-Feb_2009) [Mapping MLLT10.png]


	AF10 (10p12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

Fusion genes (updated 2016)	CDK6 (7q21.2) / MLLT10 (10p12.31)	CLP1 (11q12.1) / MLLT10 (10p12.31)	DDX3X (Xp11.4) / MLLT10 (10p12.31)
	HNRNPH1 (5q35.3) / MLLT10 (10p12.31)	KMT2A (11q23.3) / MLLT10 (10p12.31)	KMT2B (19q13.12) / MLLT10 (10p12.31)
	MLLT10 (10p12.31) / CACNA2D3 (3p21.1)	MLLT10 (10p12.31) / CDK6 (7q21.2)	MLLT10 (10p12.31) / CEP164 (11q23.3)
	MLLT10 (10p12.31) / CLP1 (11q12.1)	MLLT10 (10p12.31) / CNTNAP3B (9p11.2)	MLLT10 (10p12.31) / CYTH1 (17q25.3)
	MLLT10 (10p12.31) / DDX3X (Xp11.4)	MLLT10 (10p12.31) / KCNJ6 (21q22.13)	MLLT10 (10p12.31) / KMT2A (11q23.3)
	MLLT10 (10p12.31) / LRCH3 (3q29)	MLLT10 (10p12.31) / PICALM (11q14.2)	MLLT10 (10p12.31) / PPP2R1B (11q23.1)
	MLLT10 (10p12.31) / RACK1 (5q35.3)	MLLT10 (10p12.31) / RNF169 (11q13.4)	MLLT10 (10p12.31) / SGMS1 (10q11.23)
	MLLT10 (10p12.31) / SNAP91 (6q14.2)	MLLT10 (10p12.31) / SNTG1 (8q11.21)	NAP1L1 (12q21.2) / MLLT10 (10p12.31)
	PICALM (11q14.2) / MLLT10 (10p12.31)	SNAP91 (6q14.2) / MLLT10 (10p12.31)	USP54 (10q22.2) / MLLT10 (10p12.31)
	XPO1 (2p15) / MLLT10 (10p12.31)

DNA/RNA

Transcription

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

Protein



	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

Note

Entity	t(10;11)(p12;q23)/AML -->MLL-AF10
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 5'MLL or 3'AF10 is required in order to allow an in-frame MLL-AF10 fusion.
Hybrid/Mutated Gene	5' MLL - 3' AF10; breakpoints are at variable places along AF10
Abnormal 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	inv ins(10;11)(p12;q23q12)/AML -->MLL-AF10
Disease	One case of pediatric M5 AML
Hybrid/Mutated Gene	5' MLL - 3' AF10 and 5' AF10 - 3' HEAB, a gene at 11q12
Abnormal Protein	only MLL-AF10 is expressed


Entity	t(10;11)(p13;q14-21)-->CALM-AF10 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/Mutated 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.
Abnormal 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



Note	the breakpoint in the t(10;11)(p13;q14-21) is more in 5' of AF10

Bibliography

CALM-AF10 is a common fusion transcript in T-ALL and is specific to the TCRgammadelta lineage.

Asnafi V, Radford-Weiss I, Dastugue N, Bayle C, Leboeuf D, Charrin C, Garand R, Lafage-Pochitaloff M, Delabesse E, Buzyn A, Troussard X, Macintyre E

Blood. 2003 ; 102 (3) : 1000-1006.

PMID 12676784

Molecular basis of 11q23 rearrangements in hematopoietic malignant proliferations.

Bernard OA, Berger R

Genes, chromosomes & cancer. 1995 ; 13 (2) : 75-85.

PMID 7542910

Molecular analysis of the CALM/AF10 fusion: identical rearrangements in acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma patients.

Bohlander SK, Muschinsky V, Schrader K, Siebert R, Schlegelberger B, Harder L, Schemmel V, Fonatsch C, Ludwig WD, Hiddemann W, Dreyling MH

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000 ; 14 (1) : 93-99.

PMID 10637482

The t(10;11) translocation in acute myeloid leukemia (M5) consistently fuses the leucine zipper motif of AF10 onto the HRX gene.

Chaplin T, Bernard O, Beverloo HB, Saha V, Hagemeijer A, Berger R, Young BD

Blood. 1995 ; 86 (6) : 2073-2076.

PMID 7662954

Molecular analysis of the genomic inversion and insertion of AF10 into MLL suggests a single-step event.

Chaplin T, Jones L, Debernardi S, Hill AS, Lillington DM, Young BD

Genes, chromosomes & cancer. 2001 ; 30 (2) : 175-180.

PMID 11135434

The AF10 leucine zipper is required for leukemic transformation of myeloid progenitors by MLL-AF10.

DiMartino JF, Ayton PM, Chen EH, Naftzger CC, Young BD, Cleary ML

Blood. 2002 ; 99 (10) : 3780-3785.

PMID 11986236

MLL 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, Schrader K, Fonatsch C, Schlegelberger B, Haase D, Schoch C, Ludwig W, Löffler H, Büchner T, Wörmann B, Hiddemann W, Bohlander SK

Blood. 1998 ; 91 (12) : 4662-4667.

PMID 9616163

Identification and molecular characterisation of a CALM-AF10 fusion in acute megakaryoblastic leukaemia.

Jones LK, Chaplin T, Shankar A, Neat M, Patel N, Samuel DP, Hill AS, Debernardi S, Bassini A, Young BD, Saha V

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2001 ; 15 (6) : 910-914.

PMID 11417476

Hematologic malignancies with the t(10;11) (p13;q21) have the same molecular event and a variety of morphologic or immunologic phenotypes.

Kobayashi H, Hosoda F, Maseki N, Sakurai M, Imashuku S, Ohki M, Kaneko Y

Genes, chromosomes & cancer. 1997 ; 20 (3) : 253-259.

PMID 9365832

The t(10;11)(p12;q23) translocation in acute leukaemia: a cytogenetic and clinical study of 20 patients. European 11q23 Workshop participants.

Lillington DM, Young BD, Berger R, Martineau M, Moorman AV, Secker-Walker LM

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (5) : 801-804.

PMID 9593284

Expression pattern and cellular distribution of the murine homologue of AF10.

Linder B, Jones LK, Chaplin T, Mohd-Sarip A, Heinlein UA, Young BD, Saha V

Biochimica et biophysica acta. 1998 ; 1443 (3) : 285-296.

PMID 9878787

Biochemical analyses of the AF10 protein: the extended LAP/PHD-finger mediates oligomerisation.

Linder B, Newman R, Jones LK, Debernardi S, Young BD, Freemont P, Verrijzer CP, Saha V

Journal of molecular biology. 2000 ; 299 (2) : 369-378.

PMID 10860745

MLL-MLLT10 fusion gene in pediatric acute megakaryoblastic leukemia.

Morerio C, Rapella A, Tassano E, Rosanda C, Panarello C

Leukemia research. 2005 ; 29 (10) : 1223-1226.

PMID 16111539

11q23 rearrangements in acute leukemia.

Rubnitz JE, Behm FG, Downing JR

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1996 ; 10 (1) : 74-82.

PMID 8558942

Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia.

Van Limbergen H, Poppe B, Janssens A, De Bock R, De Paepe A, Noens L, Speleman F

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 ; 16 (3) : 344-351.

PMID 11896537

Chromosome abnormalities in leukaemia: the 11q23 paradigm.

Young BD, Saha V

Cancer surveys. 1996 ; 28 : 225-245.

PMID 8977038

Citation

This paper should be referenced as such :

Morerio, C ; Panarello, C

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

Atlas Genet Cytogenet Oncol Haematol. 2006;10(2):65-67.

Free journal version : [ pdf ] [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Genes/AF10ID4.html

History of this paper:

Huret, JL. AF10 (ALL1 fused gene from chromosome 10). Atlas Genet Cytogenet Oncol Haematol. 1997;1(2):51-52.

http://documents.irevues.inist.fr/bitstream/handle/2042/32046/12-1997-AF10ID4.pdf

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 13 ]

11q23 rearrangements (KMT2A) in de novo childhood acute myeloid leukemia
11q23 rearrangements (KMT2A) in leukaemia
11q23 rearrangements (KMT2A) in therapy related leukaemias
Infant leukaemias::Congenital leukaemias::Neonatal leukaemias
inv(7)(p15q34) TRB/HOXA10::t(7;7)(p15;q34) TRB/HOXA10
t(7;14)(p15;q11) TRD/HOXA10
t(X;10)(p11;p12) DDX3X/MLLT10
t(10;11)(p13;q21) PICALM/MLLT10
t(10;11)(p12;q23) KMT2A/MLLT10
t(10;11)(p11.2;q23) KMT2A/ABI1
t(11;17)(q23;q12-21) KMT2A/MMLT6
t(11;19)(q13;p13) FSTL3/CCND1
T-lineage acute lymphoblastic leukemia (T-ALL)

External links

	Nomenclature
HGNC (Hugo)	MLLT10 16063
	Cards
Atlas	AF10ID4
Entrez_Gene (NCBI)	MLLT10 8028 myeloid/lymphoid or mixed-lineage leukemia; translocated to, 10
Aliases	AF10
GeneCards (Weizmann)	MLLT10
Ensembl hg19 (Hinxton)	ENSG00000078403 [Gene_View]
Ensembl hg38 (Hinxton)	ENSG00000078403 [Gene_View] chr10:21534645-21743630 [Contig_View] MLLT10 [Vega]
ICGC DataPortal	ENSG00000078403
TCGA cBioPortal	MLLT10
AceView (NCBI)	MLLT10
Genatlas (Paris)	MLLT10
WikiGenes	8028
SOURCE (Princeton)	MLLT10
Genetics Home Reference (NIH)	MLLT10
	Genomic and cartography
GoldenPath hg38 (UCSC)	MLLT10 - chr10:21534645-21743630 + 10p12.31 [Description] (hg38-Dec_2013)
GoldenPath hg19 (UCSC)	MLLT10 - 10p12.31 [Description] (hg19-Feb_2009)
Ensembl	MLLT10 - 10p12.31 [CytoView hg19] MLLT10 - 10p12.31 [CytoView hg38]
Mapping of homologs : NCBI	MLLT10 [Mapview hg19] MLLT10 [Mapview hg38]
OMIM	602409
	Gene and transcription
Genbank (Entrez)	AB209755 AF060929 AF060934 AF060935 AF060936
RefSeq transcript (Entrez)	NM_001009569 NM_001195626 NM_001195627 NM_001195628 NM_001195630 NM_001324296 NM_001324297 NM_004641
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)	MLLT10
Cluster EST : Unigene	Hs.30385 [ NCBI ]
CGAP (NCI)	Hs.30385
Alternative Splicing Gallery	ENSG00000078403
Gene Expression	MLLT10 [ NCBI-GEO ] MLLT10 [ EBI - ARRAY_EXPRESS ] MLLT10 [ SEEK ] MLLT10 [ MEM ]
Gene Expression Viewer (FireBrowse)	MLLT10 [ Firebrowse - Broad ]
SOURCE (Princeton)	Expression in : [Datasets] [Normal Tissue Atlas] [carcinoma Classsification] [NCI60]
Genevisible	Expression in : [tissues] [cell-lines] [cancer] [perturbations]
BioGPS (Tissue expression)	8028
GTEX Portal (Tissue expression)	MLLT10
	Protein : pattern, domain, 3D structure
UniProt/SwissProt	P55197 [function] [subcellular_location] [family_and_domains] [pathology_and_biotech] [ptm_processing] [expression] [interaction]
NextProt	P55197 [Sequence] [Exons] [Medical] [Publications]
With graphics : InterPro	P55197
Splice isoforms : SwissVar	P55197
PhosPhoSitePlus	P55197
Domaine pattern : Prosite (Expaxy)	EPHD (PS51805) ZF_PHD_1 (PS01359) ZF_PHD_2 (PS50016)
Domains : Interpro (EBI)	Zinc_finger_PHD-type_CS Znf_FYVE_PHD Znf_PHD Znf_PHD-finger Znf_RING/FYVE/PHD
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Domain families : Smart (EMBL)	PHD (SM00249)
Conserved Domain (NCBI)	MLLT10
DMDM Disease mutations	8028
Blocks (Seattle)	MLLT10
PDB (SRS)	5DAG 5DAH
PDB (PDBSum)	5DAG 5DAH
PDB (IMB)	5DAG 5DAH
PDB (RSDB)	5DAG 5DAH
Structural Biology KnowledgeBase	5DAG 5DAH
SCOP (Structural Classification of Proteins)	5DAG 5DAH
CATH (Classification of proteins structures)	5DAG 5DAH
Superfamily	P55197
Human Protein Atlas	ENSG00000078403
Peptide Atlas	P55197
HPRD	03874
IPI	IPI00023464 IPI00941044 IPI00641100 IPI00816742 IPI00641226 IPI00550534 IPI00470780 IPI00643230 IPI00514978
	Protein Interaction databases
DIP (DOE-UCLA)	P55197
IntAct (EBI)	P55197
FunCoup	ENSG00000078403
BioGRID	MLLT10
STRING (EMBL)	MLLT10
ZODIAC	MLLT10
	Ontologies - Pathways
QuickGO	P55197
Ontology : AmiGO	DNA binding transcription factor activity, sequence-specific DNA binding protein binding nucleus nucleoplasm cytosol transcription, DNA-templated zinc ion binding protein complex positive regulation of transcription from RNA polymerase II promoter
Ontology : EGO-EBI	DNA binding transcription factor activity, sequence-specific DNA binding protein binding nucleus nucleoplasm cytosol transcription, DNA-templated zinc ion binding protein complex positive regulation of transcription from RNA polymerase II promoter
NDEx Network	MLLT10
Atlas of Cancer Signalling Network	MLLT10
Wikipedia pathways	MLLT10
	Orthology - Evolution
OrthoDB	8028
GeneTree (enSembl)	ENSG00000078403
Phylogenetic Trees/Animal Genes : TreeFam	MLLT10
HOVERGEN	P55197
HOGENOM	P55197
Homologs : HomoloGene	MLLT10
Homology/Alignments : Family Browser (UCSC)	MLLT10
	Gene fusions - Rearrangements
Fusion : Mitelman	DDX3X/MLLT10 [Xp11.4/10p12.31] [t(X;10)(p11;p12)]
Fusion : Mitelman	HNRNPH1/MLLT10 [5q35.3/10p12.31] [t(5;10)(q35;p12)]
Fusion : Mitelman	MLLT10/CEP164 [10p12.31/11q23.3] [t(10;11)(p12;q23)]
Fusion : Mitelman	MLLT10/CLP1 [10p12.31/11q12.1] [ins(10;11)(p12;q23q12)] [ins(10;11)(p12;q23q23)]

Fusion : Mitelman	MLLT10/DDX3X [10p12.31/Xp11.4] [t(X;10)(p11;p12)]
Fusion : Mitelman	MLLT10/KCNJ6 [10p12.31/21q22.13] [t(10;21)(p12;q22)]
Fusion : Mitelman	MLLT10/PICALM [10p12.31/11q14.2] [t(10;11)(p12;q14)]
Fusion : Mitelman	MLLT10/PPP2R1B [10p12.31/11q23.1] [t(10;11)(p12;q23)]
Fusion : Mitelman	MLLT10/RNF169 [10p12.31/11q13.4] [t(10;11)(p12;q13)]
Fusion : Mitelman	MLLT10/SNTG1 [10p12.31/8q11.21] [t(8;10)(q11;p12)]
Fusion : Mitelman	NAP1L1/MLLT10 [12q21.2/10p12.31] [t(10;12)(p12;q21)]
Fusion : Mitelman	PICALM/MLLT10 [11q14.2/10p12.31] [t(10;11)(p12;q14)] [t(10;11)(p12;q23)]
	[t(10;19;11)(p12;p13;q14)] [t(9;11)(p12;q14)]
Fusion : Mitelman	XPO1/MLLT10 [2p15/10p12.31] [t(2;10)(p15;p12)]
Fusion : COSMIC	KMT2A [11q23.3] - MLLT10 [10p12.31] [fusion_2033] [fusion_2034] [fusion_2035] [fusion_2036] [fusion_2037] [fusion_2038] [fusion_2039]
	[fusion_2040] [fusion_2041] [fusion_2042] [fusion_2043] [fusion_2044] [fusion_2045] [fusion_2046] [fusion_2047] [fusion_2048] [fusion_2049]
	[fusion_2050] [fusion_2051] [fusion_2052]
Fusion: TCGA	MLLT10 10p12.31 KCNJ6 21q22.13 LUAD
Fusion: TCGA	MLLT10 10p12.31 PICALM 11q14.2 LAML
Fusion: TCGA	MLLT10 10p12.31 SNTG1 8q11.21 BRCA
Fusion: TCGA	MLL MLLT10 10p12.31 LAML
Fusion: TCGA	PICALM 11q14.2 MLLT10 10p12.31 LAML
Fusion : TICdb	KMT2A [11q23.3] - MLLT10 [10p12.31]
Fusion : TICdb	PICALM [11q14.2] - MLLT10 [10p12.31]
	Polymorphisms : SNP and Copy number variants
NCBI Variation Viewer	MLLT10 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)	MLLT10
dbVar	MLLT10
ClinVar	MLLT10
1000_Genomes	MLLT10
Exome Variant Server	MLLT10
ExAC (Exome Aggregation Consortium)	MLLT10 (select the gene name)
Genetic variants : HAPMAP	8028
Genomic Variants (DGV)	MLLT10 [DGVbeta]
DECIPHER	MLLT10 [patients] [syndromes] [variants] [genes]
CONAN: Copy Number Analysis	MLLT10
	Mutations
ICGC Data Portal	MLLT10
TCGA Data Portal	MLLT10
Broad Tumor Portal	MLLT10
OASIS Portal	MLLT10 [ Somatic mutations - Copy number]
Cancer Gene: Census	MLLT10
Somatic Mutations in Cancer : COSMIC	MLLT10 [overview] [genome browser] [tissue] [distribution]
Mutations and Diseases : HGMD	MLLT10
LOVD (Leiden Open Variation Database)	Whole genome datasets
LOVD (Leiden Open Variation Database)	LOVD 3.0 shared installation
BioMuta	search MLLT10
DgiDB (Drug Gene Interaction Database)	MLLT10
DoCM (Curated mutations)	MLLT10 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)	MLLT10 (select a term)
intoGen	MLLT10
NCG5 (London)	MLLT10
Cancer3D	MLLT10(select the gene name)
Impact of mutations	[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
	Diseases
OMIM	602409
Orphanet	14434
Medgen	MLLT10
Genetic Testing Registry	MLLT10
NextProt	P55197 [Medical]
TSGene	8028
GENETests	MLLT10
Target Validation	MLLT10
Huge Navigator	MLLT10 [HugePedia]
snp3D : Map Gene to Disease	8028
BioCentury BCIQ	MLLT10
ClinGen	MLLT10
	Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD	8028
Chemical/Pharm GKB Gene	PA30849
Clinical trial	MLLT10
	Miscellaneous
canSAR (ICR)	MLLT10 (select the gene name)
	Probes
	Litterature
PubMed	41 Pubmed reference(s) in Entrez
GeneRIFs	Gene References Into Functions (Entrez)
CoreMine	MLLT10
EVEX	MLLT10
GoPubMed	MLLT10
iHOP	MLLT10

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI NCBI

indexed on : Wed Jun 7 11:55:32 CEST 2017

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