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

Other alias	AF10 (ALL1 fused gene from chromosome 10)
LocusID (NCBI)	8028
Atlas_Id	4
Location	10p12.31 [Link to chromosome band 10p12]
Location_base_pair	Starts at and ends at bp from pter


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

Fusion genes
(updated 2017)

Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

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 -->KMT2A-MLLT10
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 -->KMT2A - MLLT10
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-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/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) [ 54 ]

11q23 rearrangements (KMT2A) in therapy related leukaemias
Pediatric T-Cell Acute Lymphoblastic Leukemia
t(X;10)(p11;p12) DDX3X/MLLT10
t(10;11)(p12;q21) PICALM/MLLT10
t(10;11)(p12;q23) KMT2A/MLLT10
ins(10;11)(p12;q23q23) MLLT10/CLP1
t(2;10)(p15;p12) XPO1/MLLT10
t(5;10)(q35;p12) HNRNPH1/MLLT10
t(9;10)(p11;p12) MLLT10/CNTNAP3B
t(10;10)(p12;p13) MLLT10/FAM171A1
t(10;11)(p12;q13) MLLT10/RNF169
t(10;11)(p12;q14) MLLT10/PICALM
t(10;11)(p12;q23) MLLT10/CEP164
t(10;11)(p12;q23) MLLT10/KMT2A
t(10;11)(p12;q23) MLLT10/PPP2R1B
ins(10;11)(p12;q23q23)|ins(11;10)(q23;p12p12)|t(10;11)(p12;q23) KMT2A/MLLT10
t(10;11)(p12;q14)|t(10;11)(p12;q23) PICALM/MLLT10
t(10;12)(p12;q21) NAP1L1/MLLT10
t(10;12)(p12;q21) MLLT10/CAPS2
t(10;12)(p12;q21) NAP1L1/MLLT10
t(10;19)(p12;p13) MAP2K2/MLLT10
t(X;10)(p11;p12) MLLT10/DDX3X
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
Pediatric T-Cell Acute Lymphoblastic Leukemia
t(6;11)(q27;q23) KMT2A/AFDN
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)(p12;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)
ins(10;11)(p12;q23q23) MLLT10/CLP1
t(2;10)(p15;p12) XPO1/MLLT10
t(5;10)(q35;p12) HNRNPH1/MLLT10
t(9;10)(p11;p12) MLLT10/CNTNAP3B
t(10;10)(p12;p13) MLLT10/FAM171A1
t(10;11)(p12;q13) MLLT10/RNF169
t(10;11)(p12;q14) MLLT10/PICALM
t(10;11)(p12;q23) MLLT10/CEP164
t(10;11)(p12;q23) MLLT10/KMT2A
t(10;11)(p12;q23) MLLT10/PPP2R1B
ins(10;11)(p12;q23q23)|ins(11;10)(q23;p12p12)|t(10;11)(p12;q23) KMT2A/MLLT10
t(10;11)(p12;q14)|t(10;11)(p12;q23) PICALM/MLLT10
t(10;12)(p12;q21) NAP1L1/MLLT10
t(10;12)(p12;q21) MLLT10/CAPS2
t(10;12)(p12;q21) NAP1L1/MLLT10
t(10;19)(p12;p13) MAP2K2/MLLT10
t(X;10)(p11;p12) MLLT10/DDX3X

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]

t(8;10)(q11;p12) MLLT10/SNTG1
t(10;21)(p12;q22) MLLT10/KCNJ6

External links

	Nomenclature
	Cards
Atlas	AF10ID4.txt
Aliases
	Genomic and cartography
	Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)	Expression in : [Datasets] [Normal Tissue Atlas] [carcinoma Classsification] [NCI60]
BioGPS (Tissue expression)	8028
	Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
	Protein Interaction databases
	Ontologies - Pathways
	Clinical trials, drugs, therapy
	Miscellaneous
canSAR (ICR)	(select the gene name)
	Probes
	Litterature

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

indexed on : Thu Oct 18 17:27:26 CEST 2018

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