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

Identity

Other names	AF10 (ALL1 fused gene from chromosome 10)
HGNC	MLLT10
Location	10p12
Location_base_pair	Starts at 21863580 and ends at 22072560 bp from pter ( according to hg18-Mar_2006).
	AF10 (10p12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact rocchi@biologia.uniba.it

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

Entity	t(10;11)(p12;q23)/ANLL -->MLL-AF10
Disease	mainly M4/M5 ANLL
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)/ANLL -->MLL-AF10
Disease	One case of pediatric M5 ANLL
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

External links

	Nomenclature
HGNC	MLLT10   16063
Entrez_Gene	MLLT10  8028  myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10
	Cards
Atlas	AF10
GeneCards	MLLT10
Ensembl	ENSG00000078403 [Gene_View]  MLLT10 [Vega]
Genatlas	MLLT10
	Genomic and cartography
GoldenPath	MLLT10  -  10p12   chr10:21863580-22072560 +  10p12   [Description]    (hg18-Mar_2006)
Ensembl	MLLT10 - 10p12 [CytoView]
NCBI	Mapview
OMIM	601626 Disease map [OMIM]
OMIM	602409 Disease map [OMIM]
HomoloGene	MLLT10
	Gene and transcription
Genbank	AB209755 [ ENTREZ ]
Genbank	AF060929 [ ENTREZ ]
Genbank	AF060934 [ ENTREZ ]
Genbank	AF060935 [ ENTREZ ]
Genbank	AF060938 [ ENTREZ ]
RefSeq	NM_001009569 [ SRS ]    NM_001009569 [ ENTREZ ]
RefSeq	NM_004641 [ SRS ]    NM_004641 [ ENTREZ ]
RefSeq	AC_000053 [ SRS ]    AC_000053 [ ENTREZ ]
RefSeq	AC_000142 [ SRS ]    AC_000142 [ ENTREZ ]
RefSeq	NC_000010 [ SRS ]    NC_000010 [ ENTREZ ]
RefSeq	NT_008705 [ SRS ]    NT_008705 [ ENTREZ ]
RefSeq	NW_001837931 [ SRS ]    NW_001837931 [ ENTREZ ]
RefSeq	NW_924584 [ SRS ]    NW_924584 [ ENTREZ ]
CCDS	MLLT10 CCDS - NCBI
AceView	MLLT10 AceView - NCBI
Unigene	Hs.30385 [ SRS ]    Hs.30385 [ NCBI ]
Fast-db	5281 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	O60696 [ SRS]    O60696 [ EXPASY ]     O60696 [ INTERPRO ]     O60696 [ UNIPROT ] O60696 [ VarSplice FASTA ]
CluSTr	O60696
Blocks	O60696
HPRD	03874
	Protein Interaction databases
DIP	O60696
IntAct	O60696
	Polymorphism : SNP, mutations, diseases
OMIM	601626    [ map ]
OMIM	602409    [ map ]
GENETests	601626
GENETests	602409
SNP	MLLT10 [dbSNP-NCBI]
SNP	NM_001009569 [SNP-NCI]
SNP	NM_004641 [SNP-NCI]
SNP	MLLT10 [GeneSNPs - Utah]  MLLT10] [HGBASE - SRS]
HAPMAP	MLLT10 [HAPMAP]
COSMIC	MLLT10 [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	MLLT10 [Translocation breakpoints In Cancer]
HGMD	MLLT10
Genetic Association	MLLT10
CDC HuGE	MLLT10
	General knowledge
Family Browser	MLLT10 [UCSC Family Browser]
SOURCE	NM_001009569
SOURCE	NM_004641
SMD	Hs.30385
SAGE	Hs.30385
GO	transcription factor activity [Amigo]  transcription factor activity
GO	protein binding [Amigo]  protein binding
GO	nucleus [Amigo]  nucleus
GO	zinc ion binding [Amigo]  zinc ion binding
GO	metal ion binding [Amigo]  metal ion binding
PubGene	MLLT10
TreeFam	MLLT10
CTD	8028 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	Cancer Cytogenetics (Bari)
Probe	MLLT10 Related clones (RZPD - Berlin)
	PubMed
PubMed	17 Pubmed reference(s) in Entrez

Bibliography

Molecular basis of 11q23 rearrangements in hematopoietic malignant proliferations.

Bernard OA, Berger R

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

PMID 7542910

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

The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family.

Dreyling MH, Martinez-Climent JA, Zheng M, Mao J, Rowley JD, Bohlander SK

Proceedings of the National Academy of Sciences of the United States of America. 1996 ; 93 (10) : 4804-4809.

PMID 8643484

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

Chromosome abnormalities in leukaemia: the 11q23 paradigm.

Young BD, Saha V

Cancer surveys. 1996 ; 28 : 225-245.

PMID 8977038

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

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, Lˆffler H, Bˆșchner T, Wˆrmann B, Hiddemann W, Bohlander SK

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

PMID 9616163

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

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

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

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

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

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

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

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

MLL-MLLT10 fusion in acute monoblastic leukemia: variant complex rearrangements and 11q proximal breakpoint heterogeneity.

Morerio C, Rapella A, Rosanda C, Lanino E, Lo Nigro L, Di Cataldo A, Maserati E, Pasquali F, Panarello C

Cancer genetics and cytogenetics. 2004 ; 152 (2) : 108-112.

PMID 15262427

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

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

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Contributor(s)

Written	12-1997	Jean-Loup Huret
Updated	10-2005	Cristina Morerio, Claudio Panarello

Citation

This paper should be referenced as such :

Huret JL . MLLT10 ( myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10). Atlas Genet Cytogenet Oncol Haematol. December 1997 . URL : http://AtlasGeneticsOncology.org/Genes/AF10.html

Morerio C, Panarello C . MLLT10 ( myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10). Atlas Genet Cytogenet Oncol Haematol. October 2005 . URL : http://AtlasGeneticsOncology.org/Genes/AF10.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Sat Dec 6 17:53:27 2008