Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

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

Written1997-12Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated2005-10Cristina 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 aliasAF10 (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
AtlasAF10ID4.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 articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Oct 18 17:27:26 CEST 2018

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.