MLL (myeloid/lymphoid or mixed lineage leukemia)

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MLL (myeloid/lymphoid or mixed lineage leukemia)

Identity

Other names ALL1, HRX, Htrx (human trithorax), TRX1

HGNC MLL

Location 11q23

Location_base_pair Starts at 117812415 and ends at 117901146 bp from pter ( according to hg18-Mar_2006).

Local_order telomeric to PLZF, centromeric from RCK

MLL partner genes - Rolf Marschalek Nov 2002.

DNA/RNA

MLL (11q23) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact rocchi@biologia.uniba.it

Description 37 exons, spanning over 100 kb

Transcription in a centromeric to telomeric direction; 13 and 15 kb; coding sequence: 11.9 kb

Protein

Description 3969 amino acids; 431 KDa; contains from N-term to C-term 3 AT hooks homologous to high mobility group proteins HMGA1 and HMGA2, binding to the minor grove of DNA; 2 speckled nuclear localisation signals; 2 repression domains RD1 and RD2: RD1 or CXXC: cystein methyl transferase, binds CpG rich DNA, has a transcriptional repression activity; RD2 recruits histone desacetylases HDAC1 and 2; 3 plant homeodomains (cystein rich zinc finger domains, with homodimerization properties), 1 bromodomain (may bind acetylated histones), and 1 plant homeodomain; these domains may be involved in protein-protein interaction; a FYRN and a FRYC domain; a transactivation domain which binds CBP ; may acetylates H3 and H4 in the HOX area; a SET domain: methyltransferase; methyltates H3, including histones in the HOX area for allowing chromatin to be open to transcription. MLL is cleaved by taspase 1 into 2 proteins before entering the nucleus: a p300/320 N-term protein called MLL-N, and a p180 C-term protein, called MLL-C. The FYRN and a FRYC domains of native MLL associate MLL-N and MLL-C in a stable complex; they form a multiprotein complex with transcription factor TFIID.

Expression wide; especially in: brain, kidney, thyroid; expressed in Taned B lymphocytes and myeloid cells

Localisation nuclear, in punctate spots

Function transcriptional regulatory factor; MLL may have yin-yang functions though actions of MLL-N and MLL-C (e.g. desacetylation/acetylation); MLL-N acts as a transcriptional repressor; MLL can be associated with more than 30 proteins, including the core components of the SWI/SNF chromatin remodeling complex and the transcription complex TFIID. MLL binds promotors of HOX genes through acetylation and methylation of histones. MLL is a major regulator of hematopoesis and embryonic development, through regulation of HOX genes expression regulation ( HOXA9 in particular).

Homology trithorax (Drosophila), ALR (human), MLL2 (human)

Mutations

Note MLL is implicated in at least 10 % of acute leukaemias (AL) of various types: acute lymphoblastic leukemias (ALL), acute non lymphocytic leukemias (ANLL), biphenotypic ALs, treatment related leukemias, infant leukemias; the prognosis is poor

Implicated in

Entity t(4;11)(q21;q23)/acute leukaemias --> MLL-AFF1 (AF4)

Disease typically CD19+ CD10-precursor B-ALL, biphenotypic AL, at times ANLL (M4/M5); common in infants may be congenital; treatment related leukaemia (secondary to epipodophyllotoxins)

Prognosis median survival < 1yr

Cytogenetics additional chromosome anomalies are found in 1/4 of cases, one of which is the i(7q)

Hybrid/Mutated Gene 5' MLL-3' AF4; 12kb

Abnormal Protein 240 kDa protein with about 1400 aminoacids from NH2 MLL and 850 from COOH AF4 (variable breakpoints); the reciprocal may or may not be expressed

Entity t(6;11)(q27;q23) /ANLL -->MLL- MLLT4 (AF6)

Disease M5/M4 de novo and therapy related ANLL, T-cell ALL

Prognosis poor

Entity t(9;11) (p22;q23)/ANLL -->MLL-MLLT3 (AF9)

Disease M5/M4 de novo and therapy related ANLL

Prognosis the prognosis may not be as poor as in other 11q23 leukaemias in de novo cases; very poor prognosis in secondary ANLL cases

Cytogenetics may be overlooked; often as a sole anomaly

Hybrid/Mutated Gene variable breakpoints on both genes

Abnormal Protein N-term -- AT hook and DNA methyltransferase from MLL fused to the 192 C-term amino acids from AF9 (as breakpoints are variable, this is only an example)

Entity t(10;11)(p12;q23) /ANLL --> MLL- MLLT10 (AF10)

Disease M4 or M5 ANLL; ALL at times; therapy related ANLL

Prognosis poor

Entity t(11;19)(q23;p13.1) /ANLL --> MLL-ELL

Disease mainly M4/M5; treatment related leukemia; all ages

Prognosis very poor

Cytogenetics detected with R banding

Hybrid/Mutated Gene 5' MLL - 3' ELL

Abnormal Protein AT hook and DNA methyltransferase from MLL fused to most of ELL

Oncogenesis potential transcription factor

Entity t(11;19)(q23;p13.3) /acute leukaemias --> MLL-MLLT1 (ENL)

Disease ALL (CD19+), biphenotypic AL, ANLL (M4/M5); mainly congenital; treatment-related leukaemia

Prognosis very poor, except in rare T-cell cases

Cytogenetics detected with G banding

Hybrid/Mutated Gene 5' MLL - 3' ENL

Abnormal Protein AT hook and DNA methyltransferase from MLL fused to, most often, the nearly entire ENL

Entity Other entities:

t(X;11)(q13;q23)/ANLL, T-ALL --> MLL - AFX1

t(X;11)(q22;q23)/ANLL --> MLL- Septin2

t(1;11)(p32;q23)/ALL --> MLL- EB15 (AF1p)

t(1;11)(q21;q23)/ANLL --> MLL- MLLT11 (AF1q)

t(2;11)(q11;q23)/ALL --> MLL- AFF3 (LAF4)

t(3;11)(p21;q23)/t-ANLL, ALL--> MLL- NCKIPSD (AF3p21)

t(3;11)(q21;q23)/ALL --> MLL- EEFSEC (SELB)

t(3;11)(q25;q23)/t-ANLL --> MLL - GMPS

t(3;11)(q28;q23)/ANLL --> MLL - LPP

t(4;11)(p12;q23) --> MLL - AF4p12

t(4;11)(q12;q23) --> MLL - MIFL

t(4;11)(q21;q23)/atypical CML --> MLL - SEPT11

t(4;11)(q35;q23)--> MLL - ArgBP2

t(5;11)(q31;q23)/ANLL, ALL --> MLL - ARHGAP26 (GRAF)

ins(5;11)(q31;q13q23)/ALL --> MLL - AFF4 (AF5q31)

t(6;11)(q12;q23)/ANLL --> MLL - SMAP1

t(6;11)(q21;q23)/ANLL --> MLL - FOXO3A (AF6q21)

t(9;11)(q34;q23)/ANLL --> MLL - DAB2IP (AF9q34)

t(10;11)(p11;q23)/ANLL --> MLL - ABI1

t(10;11)(q21;q23)/ANLL --> MLL - CXXC6 (TET1)

t(11;11)(q21;q23)/ANLL --> MLL - PICALM

trisomy 11/ANLL --> MLL tandem duplication

t(11;11)(q23;q23)/ANLL --> MLL - CBL

t(11;11)(q23;q23)/ANLL --> MLL - ARHGEF12 (LARG)

t(11;11)(q23;q24)/ANLL --> MLL - TIRAP

t(11;12)(q23;q13)/ANLL --> MLL - CIP29

t(11;14)(q23;q24)/ANLL, AUL --> MLL - GPHN

t(11;15)(q23;q14)/ANLL, ALL --> MLL - CASC5 (AF15q14)

t(11;15)(q23;q14) --> MLL - MPFYVE

t(11;15)(q23;q15) --> MLL - AF15

t(11;16)(q23;p13)/MDS, ANLL, t-ANLL, ALL --> MLL - CREBBP (CBP)

t(11;17)(q23;p13)/t-ANLL --> MLL - GAS7

t(11;17)(q23;q21)/ANLL --> MLL - ACACA

t(11;17)(q23;q21)/ANLL --> MLL - LASP1

t(11;17)(q23;q21)/ ANLL --> MLL - MLLT6 (AF17)

t(11;17)(q23;q21)/ANLL --> MLL - RARa

t(11;17)(q23;q25)/ MDS, ANLL --> MLL - SEPT9 (MSF1, AF17q25)

t(11;19)(q23;p13)/ANLL --> MLL - SH3GLI1 (EEN)

t(11;19)(q23;p13)/ANLL --> MLL - MYO1F

t(11;20)(q23;q11)/ALL --> MLL - MAPRE1 (EB1)

t(11;22)(q23;q11.2)/ANLL --> MLL - SEPT5 (hCDCRel)

t(11;22)(q23;q13) /ANLL --> MLL - EP300 (P300)

Breakpoints

Note spanning a 8 kb genomic region; between exons 5 to 11; highly variable on the partner, ranging from close to the NH2-term in MLLT1 (ENL), to near the COOH-term in MLLT3 (AF9)

To be noted

the card on 11q23 rearrangements, gives an overview on diseases implicating MLL, as welle as 11q23 rearrangements in therapy related leukaemias
See also 11q23 rearrangements in childhood acute lymphoblastic leukemia: Clinical aspects and congenital leukemias

External links

	Nomenclature
HGNC	MLL 7132
Entrez_Gene	MLL 4297 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila)
	Cards
Atlas	MLL
GeneCards	MLL
Ensembl	ENSG00000118058 [Gene_View] MLL [Vega]
Genatlas	MLL
	Genomic and cartography
GoldenPath	MLL - 11q23 chr11:117812415-117901146 + 11q23 [Description] (hg18-Mar_2006)
Ensembl	MLL - 11q23 [CytoView]
NCBI	Mapview
OMIM	159555 Disease map [OMIM]
HomoloGene	MLL
	Gene and transcription
Genbank	AB209508 [ ENTREZ ]
Genbank	AF231995 [ ENTREZ ]
Genbank	AF231998 [ ENTREZ ]
Genbank	AF231999 [ ENTREZ ]
Genbank	AF232000 [ ENTREZ ]
RefSeq	NM_005933 [ SRS ] NM_005933 [ ENTREZ ]
RefSeq	AC_000054 [ SRS ] AC_000054 [ ENTREZ ]
RefSeq	AC_000143 [ SRS ] AC_000143 [ ENTREZ ]
RefSeq	NC_000011 [ SRS ] NC_000011 [ ENTREZ ]
RefSeq	NT_033899 [ SRS ] NT_033899 [ ENTREZ ]
RefSeq	NW_001838042 [ SRS ] NW_001838042 [ ENTREZ ]
RefSeq	NW_925173 [ SRS ] NW_925173 [ ENTREZ ]
CCDS	MLL CCDS - NCBI
AceView	MLL AceView - NCBI
Unigene	Hs.258855 [ SRS ] Hs.258855 [ NCBI ]
Fast-db	14280 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q03164 [ SRS] Q03164 [ EXPASY ] Q03164 [ INTERPRO ] Q03164 [ UNIPROT ] Q03164 [ VarSplice FASTA ]
Prosite	PS50014 BROMODOMAIN_2 [ SRS ] PS50014 BROMODOMAIN_2 [ Expasy ]
Prosite	PS50868 POST_SET [ SRS ] PS50868 POST_SET [ Expasy ]
Prosite	PS50280 SET [ SRS ] PS50280 SET [ Expasy ]
Prosite	PS51058 ZF_CXXC [ SRS ] PS51058 ZF_CXXC [ Expasy ]
Prosite	PS01359 ZF_PHD_1 [ SRS ] PS01359 ZF_PHD_1 [ Expasy ]
Prosite	PS50016 ZF_PHD_2 [ SRS ] PS50016 ZF_PHD_2 [ Expasy ]
Interpro	IPR000637 AT_hook_DNA_bd [ SRS ] IPR000637 AT_hook_DNA_bd [ EBI ]
Interpro	IPR001487 Bromodomain [ SRS ] IPR001487 Bromodomain [ EBI ]
Interpro	IPR003889 FYrich_C [ SRS ] IPR003889 FYrich_C [ EBI ]
Interpro	IPR003888 FYrich_N [ SRS ] IPR003888 FYrich_N [ EBI ]
Interpro	IPR016569 MeTrfase_trithorax [ SRS ] IPR016569 MeTrfase_trithorax [ EBI ]
Interpro	IPR003616 Post-SET_Zn_bd [ SRS ] IPR003616 Post-SET_Zn_bd [ EBI ]
Interpro	IPR001214 SET [ SRS ] IPR001214 SET [ EBI ]
Interpro	IPR002857 Znf_CXXC [ SRS ] IPR002857 Znf_CXXC [ EBI ]
Interpro	IPR001965 Znf_PHD [ SRS ] IPR001965 Znf_PHD [ EBI ]
Interpro	IPR013083 Znf_RING/FYVE/PHD [ SRS ] IPR013083 Znf_RING/FYVE/PHD [ EBI ]
CluSTr	Q03164
Pfam	PF02178 AT_hook [ SRS ] PF02178 AT_hook [ Sanger ] pfam02178 [ NCBI-CDD ]
Pfam	PF05965 FYRC [ SRS ] PF05965 FYRC [ Sanger ] pfam05965 [ NCBI-CDD ]
Pfam	PF05964 FYRN [ SRS ] PF05964 FYRN [ Sanger ] pfam05964 [ NCBI-CDD ]
Pfam	PF00628 PHD [ SRS ] PF00628 PHD [ Sanger ] pfam00628 [ NCBI-CDD ]
Pfam	PF00856 SET [ SRS ] PF00856 SET [ Sanger ] pfam00856 [ NCBI-CDD ]
Pfam	PF02008 zf-CXXC [ SRS ] PF02008 zf-CXXC [ Sanger ] pfam02008 [ NCBI-CDD ]
Smart	SM00384 AT_hook [EMBL]
Smart	SM00297 BROMO [EMBL]
Smart	SM00542 FYRC [EMBL]
Smart	SM00541 FYRN [EMBL]
Smart	SM00249 PHD [EMBL]
Smart	SM00508 PostSET [EMBL]
Smart	SM00317 SET [EMBL]
Blocks	Q03164
PDB	2AGH [ SRS ] 2AGH [ PdbSum ], 2AGH [ IMB ] 2AGH [ RSDB ]
PDB	2J2S [ SRS ] 2J2S [ PdbSum ], 2J2S [ IMB ] 2J2S [ RSDB ]
HPRD	01162
	Protein Interaction databases
DIP	Q03164
IntAct	Q03164
	Polymorphism : SNP, mutations, diseases
OMIM	159555 [ map ]
GENETests	159555
SNP	MLL [dbSNP-NCBI]
SNP	NM_005933 [SNP-NCI]
SNP	MLL [GeneSNPs - Utah] MLL] [HGBASE - SRS]
HAPMAP	MLL [HAPMAP]
COSMIC	MLL [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	MLL [Translocation breakpoints In Cancer]
HGMD	MLL
Genetic Association	MLL
CDC HuGE	MLL
	General knowledge
Family Browser	MLL [UCSC Family Browser]
SOURCE	NM_005933
SMD	Hs.258855
SAGE	Hs.258855
Enzyme	2.1.1.43 [ Enzyme-Expasy ] 2.1.1.43 [ Enzyme-SRS ] 2.1.1.43 [ IntEnz-EBI ] 2.1.1.43 [ BRENDA ] 2.1.1.43 [ KEGG ]
GO	DNA binding [Amigo] DNA binding
GO	transcription factor activity [Amigo] transcription factor activity
GO	RNA polymerase II transcription factor activity [Amigo] RNA polymerase II transcription factor activity
GO	protein binding [Amigo] protein binding
GO	GTP binding [Amigo] GTP binding
GO	nucleus [Amigo] nucleus
GO	DNA repair [Amigo] DNA repair
GO	DNA recombination [Amigo] DNA recombination
GO	transcription [Amigo] transcription
GO	regulation of transcription, DNA-dependent [Amigo] regulation of transcription, DNA-dependent
GO	transcription from RNA polymerase II promoter [Amigo] transcription from RNA polymerase II promoter
GO	protein complex assembly [Amigo] protein complex assembly
GO	apoptosis [Amigo] apoptosis
GO	cell cycle [Amigo] cell cycle
GO	methyltransferase activity [Amigo] methyltransferase activity
GO	zinc ion binding [Amigo] zinc ion binding
GO	chromatin modification [Amigo] chromatin modification
GO	transferase activity [Amigo] transferase activity
GO	histone-lysine N-methyltransferase activity [Amigo] histone-lysine N-methyltransferase activity
GO	embryonic hemopoiesis [Amigo] embryonic hemopoiesis
GO	protein homodimerization activity [Amigo] protein homodimerization activity
GO	metal ion binding [Amigo] metal ion binding
PubGene	MLL
TreeFam	MLL
CTD	4297 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	MLL1 (11q23) in normal cells (Bari)
Probe	MLL Related clones (RZPD - Berlin)
	PubMed
PubMed	143 Pubmed reference(s) in Entrez

Bibliography

Self-fusion of the ALL1 gene. A new genetic mechanism for acute leukemia.

Schichman SA, Canaani E, Croce CM

JAMA : the journal of the American Medical Association. 1995 ; 273 (7) : 571-576.

PMID 7837391

Molecular basis of 11q23 rearrangements in hematopoietic malignant proliferations.

Bernard OA, Berger R

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

PMID 7542910

Complete exon structure of the ALL1 gene.

Rasio D, Schichman SA, Negrini M, Canaani E, Croce CM

Cancer research. 1996 ; 56 (8) : 1766-1769.

PMID 8620491

Exon/intron structure of the human ALL-1 (MLL) gene involved in translocations to chromosomal region 11q23 and acute leukaemias.

Nilson I, L��chner K, Siegler G, Greil J, Beck JD, Fey GH, Marschalek R

British journal of haematology. 1996 ; 93 (4) : 966-972.

PMID 8703835

Chromosome abnormalities in leukaemia: the 11q23 paradigm.

Young BD, Saha V

Cancer surveys. 1996 ; 28 : 225-245.

PMID 8977038

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

Structure and expression pattern of human ALR, a novel gene with strong homology to ALL-1 involved in acute leukemia and to Drosophila trithorax.

Prasad R, Zhadanov AB, Sedkov Y, Bullrich F, Druck T, Rallapalli R, Yano T, Alder H, Croce CM, Huebner K, Mazo A, Canaani E

Oncogene. 1997 ; 15 (5) : 549-560.

PMID 9247308

Disruption of a homolog of trithorax by 11q23 translocations: leukemogenic and transcriptional implications.

Waring PM, Cleary ML

Current topics in microbiology and immunology. 1997 ; 220 : 1-23.

PMID 9103672

Mll rearrangements in haematological malignancies: lessons from clinical and biological studies.

Dimartino JF, Cleary ML

British journal of haematology. 1999 ; 106 (3) : 614-626.

PMID 10468849

MLL2, the second human homolog of the Drosophila trithorax gene, maps to 19q13.1 and is amplified in solid tumor cell lines.

Huntsman DG, Chin SF, Muleris M, Batley SJ, Collins VP, Wiedemann LM, Aparicio S, Caldas C

Oncogene. 1999 ; 18 (56) : 7975-7984.

PMID 10637508

REVIEW articles automatic search in PubMed

Last year publications automatic search in PubMed

Search in all EBI NCBI

Contributor(s)

Written 12-1997 Jean-Loup Huret

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

Updated 12-2000 Jay L Hess, Jean-Loup Huret

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

Updated 11-2002 Rolf Marschalek

Instituts für Pharmazeutische Biologie, JWG Universitaet Frankfurt/Main, Biozentrum, N230, 303, Marie Curie Str. 9, D-60439 Frankfurt/Main, Germany

Updated 10-2005 Jean-Loup Huret

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

Citation

This paper should be referenced as such :
Huret JL . MLL (myeloid/lymphoid or mixed lineage leukemia). Atlas Genet Cytogenet Oncol Haematol. December 1997 .
URL : http://AtlasGeneticsOncology.org/Genes/MLL.html

Hess JL and Huret JL . MLL (myeloid/lymphoid or mixed lineage leukemia). Atlas Genet Cytogenet Oncol Haematol. December 2000 .
URL : http://AtlasGeneticsOncology.org/Genes/MLL.html

Marschalek R . MLL (myeloid/lymphoid or mixed lineage leukemia). Atlas Genet Cytogenet Oncol Haematol. November 2002 .
URL : http://AtlasGeneticsOncology.org/Genes/MLL.html

Huret JL . MLL (myeloid/lymphoid or mixed lineage leukemia). Atlas Genet Cytogenet Oncol Haematol. October 2005 .
URL : http://AtlasGeneticsOncology.org/Genes/MLL.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Nov 27 13:25:42 2008

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

For comments and suggestions or contributions, please contact us
jlhuret@AtlasGeneticsOncology.org.

Other names	ALL1, HRX, Htrx (human trithorax), TRX1
HGNC	MLL
Location	11q23
Location_base_pair	Starts at 117812415 and ends at 117901146 bp from pter ( according to hg18-Mar_2006).
Local_order	telomeric to PLZF, centromeric from RCK


	MLL partner genes - Rolf Marschalek Nov 2002.



	MLL (11q23) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact rocchi@biologia.uniba.it

Description	37 exons, spanning over 100 kb
Transcription	in a centromeric to telomeric direction; 13 and 15 kb; coding sequence: 11.9 kb



Description	3969 amino acids; 431 KDa; contains from N-term to C-term 3 AT hooks homologous to high mobility group proteins HMGA1 and HMGA2, binding to the minor grove of DNA; 2 speckled nuclear localisation signals; 2 repression domains RD1 and RD2: RD1 or CXXC: cystein methyl transferase, binds CpG rich DNA, has a transcriptional repression activity; RD2 recruits histone desacetylases HDAC1 and 2; 3 plant homeodomains (cystein rich zinc finger domains, with homodimerization properties), 1 bromodomain (may bind acetylated histones), and 1 plant homeodomain; these domains may be involved in protein-protein interaction; a FYRN and a FRYC domain; a transactivation domain which binds CBP ; may acetylates H3 and H4 in the HOX area; a SET domain: methyltransferase; methyltates H3, including histones in the HOX area for allowing chromatin to be open to transcription. MLL is cleaved by taspase 1 into 2 proteins before entering the nucleus: a p300/320 N-term protein called MLL-N, and a p180 C-term protein, called MLL-C. The FYRN and a FRYC domains of native MLL associate MLL-N and MLL-C in a stable complex; they form a multiprotein complex with transcription factor TFIID.
Expression	wide; especially in: brain, kidney, thyroid; expressed in Taned B lymphocytes and myeloid cells
Localisation	nuclear, in punctate spots
Function	transcriptional regulatory factor; MLL may have yin-yang functions though actions of MLL-N and MLL-C (e.g. desacetylation/acetylation); MLL-N acts as a transcriptional repressor; MLL can be associated with more than 30 proteins, including the core components of the SWI/SNF chromatin remodeling complex and the transcription complex TFIID. MLL binds promotors of HOX genes through acetylation and methylation of histones. MLL is a major regulator of hematopoesis and embryonic development, through regulation of HOX genes expression regulation ( HOXA9 in particular).
Homology	trithorax (Drosophila), ALR (human), MLL2 (human)

Entity	t(4;11)(q21;q23)/acute leukaemias --> MLL-AFF1 (AF4)
Disease	typically CD19+ CD10-precursor B-ALL, biphenotypic AL, at times ANLL (M4/M5); common in infants may be congenital; treatment related leukaemia (secondary to epipodophyllotoxins)
Prognosis	median survival < 1yr
Cytogenetics	additional chromosome anomalies are found in 1/4 of cases, one of which is the i(7q)
Hybrid/Mutated Gene	5' MLL-3' AF4; 12kb
Abnormal Protein	240 kDa protein with about 1400 aminoacids from NH2 MLL and 850 from COOH AF4 (variable breakpoints); the reciprocal may or may not be expressed

Entity	t(6;11)(q27;q23) /ANLL -->MLL- MLLT4 (AF6)
Disease	M5/M4 de novo and therapy related ANLL, T-cell ALL
Prognosis	poor

Entity	t(9;11) (p22;q23)/ANLL -->MLL-MLLT3 (AF9)
Disease	M5/M4 de novo and therapy related ANLL
Prognosis	the prognosis may not be as poor as in other 11q23 leukaemias in de novo cases; very poor prognosis in secondary ANLL cases
Cytogenetics	may be overlooked; often as a sole anomaly
Hybrid/Mutated Gene	variable breakpoints on both genes
Abnormal Protein	N-term -- AT hook and DNA methyltransferase from MLL fused to the 192 C-term amino acids from AF9 (as breakpoints are variable, this is only an example)

Entity	t(10;11)(p12;q23) /ANLL --> MLL- MLLT10 (AF10)
Disease	M4 or M5 ANLL; ALL at times; therapy related ANLL
Prognosis	poor

Entity	t(11;19)(q23;p13.1) /ANLL --> MLL-ELL
Disease	mainly M4/M5; treatment related leukemia; all ages
Prognosis	very poor
Cytogenetics	detected with R banding
Hybrid/Mutated Gene	5' MLL - 3' ELL
Abnormal Protein	AT hook and DNA methyltransferase from MLL fused to most of ELL
Oncogenesis	potential transcription factor

Entity	t(11;19)(q23;p13.3) /acute leukaemias --> MLL-MLLT1 (ENL)
Disease	ALL (CD19+), biphenotypic AL, ANLL (M4/M5); mainly congenital; treatment-related leukaemia
Prognosis	very poor, except in rare T-cell cases
Cytogenetics	detected with G banding
Hybrid/Mutated Gene	5' MLL - 3' ENL
Abnormal Protein	AT hook and DNA methyltransferase from MLL fused to, most often, the nearly entire ENL

Entity	Other entities: t(X;11)(q13;q23)/ANLL, T-ALL --> MLL - AFX1 t(X;11)(q22;q23)/ANLL --> MLL- Septin2 t(1;11)(p32;q23)/ALL --> MLL- EB15 (AF1p) t(1;11)(q21;q23)/ANLL --> MLL- MLLT11 (AF1q) t(2;11)(q11;q23)/ALL --> MLL- AFF3 (LAF4) t(3;11)(p21;q23)/t-ANLL, ALL--> MLL- NCKIPSD (AF3p21) t(3;11)(q21;q23)/ALL --> MLL- EEFSEC (SELB) t(3;11)(q25;q23)/t-ANLL --> MLL - GMPS t(3;11)(q28;q23)/ANLL --> MLL - LPP t(4;11)(p12;q23) --> MLL - AF4p12 t(4;11)(q12;q23) --> MLL - MIFL t(4;11)(q21;q23)/atypical CML --> MLL - SEPT11 t(4;11)(q35;q23)--> MLL - ArgBP2 t(5;11)(q31;q23)/ANLL, ALL --> MLL - ARHGAP26 (GRAF) ins(5;11)(q31;q13q23)/ALL --> MLL - AFF4 (AF5q31) t(6;11)(q12;q23)/ANLL --> MLL - SMAP1 t(6;11)(q21;q23)/ANLL --> MLL - FOXO3A (AF6q21) t(9;11)(q34;q23)/ANLL --> MLL - DAB2IP (AF9q34) t(10;11)(p11;q23)/ANLL --> MLL - ABI1 t(10;11)(q21;q23)/ANLL --> MLL - CXXC6 (TET1) t(11;11)(q21;q23)/ANLL --> MLL - PICALM trisomy 11/ANLL --> MLL tandem duplication t(11;11)(q23;q23)/ANLL --> MLL - CBL t(11;11)(q23;q23)/ANLL --> MLL - ARHGEF12 (LARG) t(11;11)(q23;q24)/ANLL --> MLL - TIRAP t(11;12)(q23;q13)/ANLL --> MLL - CIP29 t(11;14)(q23;q24)/ANLL, AUL --> MLL - GPHN t(11;15)(q23;q14)/ANLL, ALL --> MLL - CASC5 (AF15q14) t(11;15)(q23;q14) --> MLL - MPFYVE t(11;15)(q23;q15) --> MLL - AF15 t(11;16)(q23;p13)/MDS, ANLL, t-ANLL, ALL --> MLL - CREBBP (CBP) t(11;17)(q23;p13)/t-ANLL --> MLL - GAS7 t(11;17)(q23;q21)/ANLL --> MLL - ACACA t(11;17)(q23;q21)/ANLL --> MLL - LASP1 t(11;17)(q23;q21)/ ANLL --> MLL - MLLT6 (AF17) t(11;17)(q23;q21)/ANLL --> MLL - RARa t(11;17)(q23;q25)/ MDS, ANLL --> MLL - SEPT9 (MSF1, AF17q25) t(11;19)(q23;p13)/ANLL --> MLL - SH3GLI1 (EEN) t(11;19)(q23;p13)/ANLL --> MLL - MYO1F t(11;20)(q23;q11)/ALL --> MLL - MAPRE1 (EB1) t(11;22)(q23;q11.2)/ANLL --> MLL - SEPT5 (hCDCRel) t(11;22)(q23;q13) /ANLL --> MLL - EP300 (P300)



Note	spanning a 8 kb genomic region; between exons 5 to 11; highly variable on the partner, ranging from close to the NH2-term in MLLT1 (ENL), to near the COOH-term in MLLT3 (AF9)

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

Written	12-1997	Jean-Loup Huret
		Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated	12-2000	Jay L Hess, Jean-Loup Huret
		Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated	11-2002	Rolf Marschalek
		Instituts für Pharmazeutische Biologie, JWG Universitaet Frankfurt/Main, Biozentrum, N230, 303, Marie Curie Str. 9, D-60439 Frankfurt/Main, Germany
Updated	10-2005	Jean-Loup Huret
		Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France