AML1 (acute myeloid leukemia 1)

RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene))

CBFA2 (core binding factor A2)

Identity

Other names	PEBPaB (polyomavirus enhancer binding protein aB)
HGNC	RUNX1
Location	21q22.3
Location_base_pair	Starts at 35081968 and ends at 35182857 bp from pter (hg18-Mar_2006).
	AML1 (21q22.3) in normal cells: clone dJ1107L6 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are wellcome: contact M Rocchi

DNA/RNA

	DNA Diagram
Description	the gene spans a region of more than 120 kb
Transcription	transcription is from telomere to centromere --> the fusion gene is located on the 'other' chromosome (eg the der(8) of the t(8;21), the der(3) of the t(3;21)...); alternate splicing --> transcripts of 2, 3.3, ->7.5 and 8 kb

Protein

	Protein Diagram
Description	250, 453 amino acids and other forms; forms heterodimers with CBFB
Expression	widely expressed, including hematopoietic cells at various stages of differenciation: role in haematopoiesis
Localisation	nuclear
Function	transcription factor (activator) for various hematopoietic-specific genes: binds to the core site 5' PyGPyGGTPy 3' of a number of promotors and enhancers, as in GM-CSF (granulocyte-macrophage colony stimulating factor, CSF1R (colony stimulating factor 1 receptor), TCRb sites (T cell antigen receptors), and myeloid myeloperoxidase
Homology	1- Runt (drosophila): nuclear DNA binding protein; role in segmentation (embryology); 2- AML2 (also called: CBFA3, CBFa3, PEBPaC), located in 1p35-36, expressed in B lineage (3 and 5 kb RNA); AML3: (also called: CBFA1, CBFa1, PEBPaA) in 6p21; 3- cbfa family (mouse)

Implicated in

Entity	Familial platelet disorder with predisposition to acute non lymphocytic leukemia
Entity	t(1;21)(p36;q22) treatment related acute non lymphocytic leukemia (ANLL) --> ?/ AML1
Entity	t(2;21)(p11;q22) ANLL --> ?/ AML1
Entity	t(3;21)(q26;q22)/ myelodysplastic syndrome (MDS) or ANLL --> -EVI1 or EAP/ MDS1 - AML1
Disease	CML-BC of myeloid type; ANLL and MDS, often therapy related (secondary to antitopoisomerase II)
Hybrid/Mutated Gene	5' AML1 - 3' EAP or MDS1 or EVI1
Entity	t(4;21)(q31;q22) T-cell acute lymphoblastic leukemia (T-ALL) --> ?/ AML1
Entity	t(5;21)(q13;q22) myelodysplastic syndrome (MDS) and ANLL --> ?/ AML1
Entity	t(8;21)(q22;q22)/ANLL. --> ETO - AML1
Disease	ANLL, M2 mostly
Prognosis	CR is obtained; median survival (1.5-2 yrs) is the range with other ANLL or relatively better
Cytogenetics	additional anomalies are frequent: loss of Y or X chromosome, del(7q)/-7, +8, del (9q); complex t(8;21;Var) are known and have revealed that the crucial event lies on der(8); in agrement with the fact that both genes are transcribed from telomere to centromere
Hybrid/Mutated Gene	5' AML1 - 3' ETO
Abnormal Protein	N-term AML1 with the Runt domain fused to the nearly entire ETO
Oncogenesis	the fusion protein retain the ability to recognize the AML1 concensus binding site (--> negative dominant competitor with the normal AML1) and to dimerize with the cbtb/CBTB subunit --> probable altered transcriptional regulation of normal AML1 target genes
Entity	t(8;21)(q23;q22) MDS --> FOG2 / AML1
Entity	t(8;21)(q24;q22) ALL and ANLL --> TRPS1 / AML1
Entity	t(12;21)(p13;q22)/ALL --> ETV6-AML1
Disease	B cell ALL (CD10+)
Prognosis	CR in all cases; prognosis seems good
Cytogenetics	often undetectable without FISH; additional anomalies: frequent del(12)(p12) on the other allele
Hybrid/Mutated Gene	5' ETV6 - 3' AML1on the der(21)
Abnormal Protein	Helix loop helix of TEL fused to the nearly entire AML1 protein; the other TEL allele is often deleted
Entity	t(12;21)(q24;q22) ANLL --> ?/ AML1
Entity	t(16;21)(q24;q22) ANLL --> MTG16-AML1
Disease	ANLL and therapy related ANLL; mainly with preceeding MDS
Prognosis	very poor
Entity	t(17;21)(q11;q22) ANLL
Entity	t(19;21)(q13;q22) treatment related ANLL --> AMP19 / AML1
Entity	t(20;21)(q1;3q22) treatment related ANL --> ? / AML1
Entity	t(21;21)(q11;q22) MDS --> UPS25 / AML1

Breakpoints

External links

	Nomenclature
HGNC	RUNX1   10471
Entrez_Gene	RUNX1  861  runt-related transcription factor 1
	Cards
Atlas	AML1
GeneCards	RUNX1
Ensembl	RUNX1 [Search_View]   ENSG00000159216 [Gene_View]
Genatlas	RUNX1
GeneLynx	RUNX1
eGenome	RUNX1
euGene	861
	Genomic and cartography
GoldenPath	RUNX1  -  21q22.3   chr21:35081968-35182857 -  21q22.3   [Description]    (hg18-Mar_2006)
Ensembl	RUNX1 - 21q22.3 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	RUNX1
	Gene and transcription
Genbank	AA878154 [ ENTREZ ]
Genbank	AK226159 [ ENTREZ ]
Genbank	AK310587 [ ENTREZ ]
Genbank	AL581043 [ ENTREZ ]
Genbank	AV761975 [ ENTREZ ]
RefSeq	NM_001001890 [ SRS ]    NM_001001890 [ ENTREZ ]
RefSeq	NM_001122607 [ SRS ]    NM_001122607 [ ENTREZ ]
RefSeq	NM_001754 [ SRS ]    NM_001754 [ ENTREZ ]
RefSeq	AC_000064 [ SRS ]    AC_000064 [ ENTREZ ]
RefSeq	AC_000153 [ SRS ]    AC_000153 [ ENTREZ ]
RefSeq	NC_000021 [ SRS ]    NC_000021 [ ENTREZ ]
RefSeq	NT_011512 [ SRS ]    NT_011512 [ ENTREZ ]
RefSeq	NW_001838706 [ SRS ]    NW_001838706 [ ENTREZ ]
RefSeq	NW_927384 [ SRS ]    NW_927384 [ ENTREZ ]
AceView	RUNX1 AceView - NCBI
Unigene	Hs.612648 [ SRS ]    Hs.612648 [ NCBI ]     HS612648 [ spliceNest ]
Fast-db	2368 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q01196 [ SRS]    Q01196 [ EXPASY ]     Q01196 [ INTERPRO ]     Q01196 [ UNIPROT ]
Prosite	PS51062 RUNT [ SRS ]    PS51062 RUNT [ Expasy ]
Interpro	IPR013524 AML1/Runt_N [ SRS ]    IPR013524 AML1/Runt_N [ EBI ]
Interpro	IPR000040 AML1_Runt [ SRS ]    IPR000040 AML1_Runt [ EBI ]
Interpro	IPR012346 p53_RUNT_DNA_bd [ SRS ]    IPR012346 p53_RUNT_DNA_bd [ EBI ]
Interpro	IPR013711 RunxI [ SRS ]    IPR013711 RunxI [ EBI ]
Interpro	IPR016554 TF_Runt-rel_RUNX [ SRS ]    IPR016554 TF_Runt-rel_RUNX [ EBI ]
CluSTr	Q01196
Pfam	PF00853 Runt [ SRS ]    PF00853 Runt [ Sanger ]    pfam00853 [ NCBI-CDD ]
Pfam	PF08504 RunxI [ SRS ]    PF08504 RunxI [ Sanger ]    pfam08504 [ NCBI-CDD ]
Blocks	Q01196
PDB	1CMO [ SRS ]    1CMO [ PdbSum ],   1CMO [ IMB ]   1CMO [ RSDB ]
PDB	1CO1 [ SRS ]    1CO1 [ PdbSum ],   1CO1 [ IMB ]   1CO1 [ RSDB ]
PDB	1E50 [ SRS ]    1E50 [ PdbSum ],   1E50 [ IMB ]   1E50 [ RSDB ]
PDB	1H9D [ SRS ]    1H9D [ PdbSum ],   1H9D [ IMB ]   1H9D [ RSDB ]
PDB	1LJM [ SRS ]    1LJM [ PdbSum ],   1LJM [ IMB ]   1LJM [ RSDB ]
HPRD	01043
	Protein Interaction databases
DIP	Q01196
IntAct	Q01196
	Polymorphism : SNP, mutations, diseases
OMIM	151385;180300;601399;601626    [ map ]
GENECLINICS	151385;180300;601399;601626
SNP	RUNX1 [dbSNP-NCBI]
SNP	NM_001001890 [SNP-NCI]
SNP	NM_001122607 [SNP-NCI]
SNP	NM_001754 [SNP-NCI]
SNP	RUNX1 [GeneSNPs - Utah]  RUNX1] [HGBASE - SRS]
HAPMAP	RUNX1 [HAPMAP]
COSMIC	RUNX1 [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	RUNX1 [Translocation breakpoints In Cancer]
HGMD	RUNX1
	General knowledge
Family Browser	RUNX1 [UCSC Family Browser]
SOURCE	NM_001001890
SOURCE	NM_001122607
SOURCE	NM_001754
SMD	Hs.612648
SAGE	Hs.612648
GO	molecular_function [Amigo]  molecular_function
GO	transcription factor activity [Amigo]  transcription factor activity
GO	protein binding [Amigo]  protein binding
GO	ATP binding [Amigo]  ATP binding
GO	cellular_component [Amigo]  cellular_component
GO	nucleus [Amigo]  nucleus
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	multicellular organismal development [Amigo]  multicellular organismal development
GO	biological_process [Amigo]  biological_process
GO	transcription activator activity [Amigo]  transcription activator activity
GO	positive regulation of granulocyte differentiation [Amigo]  positive regulation of granulocyte differentiation
GO	chloride ion binding [Amigo]  chloride ion binding
GO	positive regulation of angiogenesis [Amigo]  positive regulation of angiogenesis
GO	positive regulation of transcription from RNA polymerase II promoter [Amigo]  positive regulation of transcription from RNA polymerase II promoter
PubGene	RUNX1
TreeFam	RUNX1
CTD	861 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	AML1 (21q22.3) in normal cells (Bari)
Probe	RUNX1 Related clones (RZPD - Berlin)
	PubMed
PubMed	206 Pubmed reference(s) in Entrez

Bibliography

Molecular basis of the t(8;21) translocation in acute myeloid leukaemia.

Ohki M

Seminars in cancer biology. 1993 ; 4 (6) : 369-375.

PMID 8142622

AML1 and the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia.

Nucifora G, Rowley JD

Blood. 1995 ; 86 (1) : 1-14.

PMID 7795214

High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia.

Romana SP, Poirel H, Leconiat M, Flexor MA, Mauchauffˆ© M, Jonveaux P, Macintyre EA, Berger R, Bernard OA

Blood. 1995 ; 86 (11) : 4263-4269.

PMID 7492786

CBFA2(AML1) translocations with novel partner chromosomes in myeloid leukemias: association with prior therapy.

Roulston D, Espinosa R 3rd, Nucifora G, Larson RA, Le Beau MM, Rowley JD

Blood. 1998 ; 92 (8) : 2879-2885.

PMID 9763573

Combined spectral karyotyping and DAPI banding analysis of chromosome abnormalities in myelodysplastic syndrome.

Kakazu N, Taniwaki M, Horiike S, Nishida K, Tatekawa T, Nagai M, Takahashi T, Akaogi T, Inazawa J, Ohki M, Abe T

Genes, chromosomes & cancer. 1999 ; 26 (4) : 336-345.

PMID 10534769

A new angle on a pervasive oncogene.

Cleary ML

Nature genetics. 1999 ; 23 (2) : 134-135.

PMID 10508502

Concurrent translocations of MLL and CBFA2 (AML1) genes with new partner breakpoints in a child with secondary myelodysplastic syndrome after treatment of acute lymphoblastic leukemia.

Mathew S, Head D, Rubnitz JE, Raimondi SC

Genes, chromosomes & cancer. 2000 ; 28 (2) : 227-232.

PMID 10825008

Identification of two new translocations that disrupt the AML1 gene.

Richkind K, Hromas R, Lytle C, Crenshaw D, Velasco J, Roherty S, Srinivasiah J, Varella-Garcia M

Cancer genetics and cytogenetics. 2000 ; 122 (2) : 141-143.

PMID 11106827

A novel syndrome of radiation-associated acute myeloid leukemia involving AML1 gene translocations.

Hromas R, Shopnick R, Jumean HG, Bowers C, Varella-Garcia M, Richkind K

Blood. 2000 ; 95 (12) : 4011-4013.

PMID 10845943

A novel CBFA2 single-nucleotide mutation in familial platelet disorder with propensity to develop myeloid malignancies.

Buijs A, Poddighe P, van Wijk R, van Solinge W, Borst E, Verdonck L, Hagenbeek A, Pearson P, Lokhorst H

Blood. 2001 ; 98 (9) : 2856-2858.

PMID 11675361

Novel cryptic, complex rearrangements involving ETV6-CBFA2 (TEL-AML1) genes identified by fluorescence in situ hybridization in pediatric patients with acute lymphoblastic leukemia.

Mathew S, Shurtleff SA, Raimondi SC

Genes, chromosomes & cancer. 2001 ; 32 (2) : 188-193.

PMID 11550288

AML1-TRPS1 chimeric protein is generated by t(8;21)(q24;q22) in relapsing acute myeloblastic leukemia.

Asou N, Matsuno N, Mitsuya H

Am Soc Hematol,. 1943.

In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis.

Michaud J, Wu F, Osato M, Cottles GM, Yanagida M, Asou N, Shigesada K, Ito Y, Benson KF, Raskind WH, Rossier C, Antonarakis SE, Israels S, McNicol A, Weiss H, Horwitz M, Scott HS

Blood. 2002 ; 99 (4) : 1364-1372.

PMID 11830488

A new translocation that rearranges the AML1 gene in a patient with T-cell acute lymphoblastic leukemia.

Mikhail FM, Serry KA, Hatem N, Mourad ZI, Farawela HM, El Kaffash DM, Coignet L, Nucifora G

Cancer genetics and cytogenetics. 2002 ; 135 (1) : 96-100.

PMID 12072207

High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia.

Romana SP, et al.

Blood. 1995 Dec 1;86(11):4263-9.

PMID 7492786

CBFA2(AML1) Translocations With Novel Partner Chromosomes in Myeloid Leukemias: Association With Prior Therapy.

Roulston D, Espinosa IIIR, Nucifora G, Larson RA, Le Beau MM, Rowley JD.

Blood 1998; 92: 2879-2885.

Combined spectral karyotyping and DAPI banding analysis of chromosome abnormalities in myelodysplastic syndrome.

Kakazu N, Taniwaki M, Horiike S, Nishida K, Tatekawa T, Nagai M, Takahashi T, Akaogi T, Inazawa J, Ohki M, Abe T.

Genes Chromosomes Cancer 1999; 26: 336-345.

Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia.

Song WJ, Sullivan MG, Legare RD, Hutchings S, Tan X, Kufrin D, Ratajczak J, Resende IC, Haworth C, Hock R, Loh M, Felix C, Roy DC, Busque L, Kurnit D, Willman C, Gewirtz AM, Speck NA, Bushweller JH, Li FP, Gardiner K, Poncz M, Maris JM, Gilliland DG.

Nat Genet. 1999;23:134-135.

Concurrent translocations of MLL and CBFA2 (AML1) genes with new partner breakpoints in a child with secondary myelodysplastic syndrome after treatment of acute lymphoblastic leukemia.

Mathew S, Head D, Rubnitz JE, Raimondi SC.

Genes Chromosomes Cancer 2000; 28: 227-232.

PMID 10825008

Identification of two new translocations that disrupt the AML1 gene.

Richkind K, Hromas R, Lytle C, Crenshaw D, Velasco J, Roherty S, Srinivasiah J, Varella-Garcia M.

Cancer Genet Cytogenet 2000; 122: 141-143.

A novel syndrome of radiation-associated acute myeloid leukemia involving AML1 gene translocations

Hromas R, Shopnick R, Jumean HG, Bowers C, Varella-Garcia M, Richkind K.

Blood 2000; 95:4011-4013

A novel CBFA2 single-nucleotide mutation in familial platelet disorder with propensity to develop myeloid malignancies.

Buijs A, Poddighe P, van Wijk R, van Solinge W, Borst E, Verdonck L, Hagenbeek A, Pearson P, Lokhorst H.

Blood 2001; 98:2856-2858.

Novel cryptic, complex rearrangements involving ETV6-CBFA2 (TEL-AML1) genes identified by fluorescence in situ hybridization in pediatric patients with acute lymphoblastic leukemia.

Mathew S, Shurtleff SA, Raimondi SC.

Genes Chromosomes Cancer. 2001; 32: 188-193.

PMID 11550288

AML1-TRPS1 chimeric protein is generated by t(8;21)(q24;q22) in relapsing acute myeloblastic leukemia.

Asou N, Matsuno N, Mitsuya H.

Am Soc Hematol, 43 Annual meeting, Blood 2001; 98 11: 564a.

In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis.

Michaud J, Wu F, Osato M, Cottles GM, Yanagida M, Asou N, Shigesada K, Ito Y, Benson KF, Raskind WH, Rossier C, Antonarakis SE, Israels S, McNicol A, Weiss H, Horwitz M, Scott HS.

Blood 2002;99:1364-1372.

A new translocation that rearranges the AML1 gene in a patient with T-cell acute lymphoblastic leukemia.

Mikhail FM, Serry KA, Hatem N, Mourad ZI, Farawela HM, El Kaffash DM, Coignet L, Nucifora G.

Cancer Genet Cytogenet 2002; 135: 96-100.

Molecular basis of the t(8;21) translocation in acute myeloid leukaemia.

Ohki M

Seminars in cancer biology. 1993 ; 4 (6) : 369-375.

PMID 8142622

AML1 and the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia.

Nucifora G, Rowley JD

Blood. 1995 ; 86 (1) : 1-14.

PMID 7795214

High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia.

Romana SP, Poirel H, Leconiat M, Flexor MA, Mauchauffˆ© M, Jonveaux P, Macintyre EA, Berger R, Bernard OA

Blood. 1995 ; 86 (11) : 4263-4269.

PMID 7492786

CBFA2(AML1) translocations with novel partner chromosomes in myeloid leukemias: association with prior therapy.

Roulston D, Espinosa R 3rd, Nucifora G, Larson RA, Le Beau MM, Rowley JD

Blood. 1998 ; 92 (8) : 2879-2885.

PMID 9763573

Combined spectral karyotyping and DAPI banding analysis of chromosome abnormalities in myelodysplastic syndrome.

Kakazu N, Taniwaki M, Horiike S, Nishida K, Tatekawa T, Nagai M, Takahashi T, Akaogi T, Inazawa J, Ohki M, Abe T

Genes, chromosomes & cancer. 1999 ; 26 (4) : 336-345.

PMID 10534769

A new angle on a pervasive oncogene.

Cleary ML

Nature genetics. 1999 ; 23 (2) : 134-135.

PMID 10508502

Concurrent translocations of MLL and CBFA2 (AML1) genes with new partner breakpoints in a child with secondary myelodysplastic syndrome after treatment of acute lymphoblastic leukemia.

Mathew S, Head D, Rubnitz JE, Raimondi SC

Genes, chromosomes & cancer. 2000 ; 28 (2) : 227-232.

PMID 10825008

Identification of two new translocations that disrupt the AML1 gene.

Richkind K, Hromas R, Lytle C, Crenshaw D, Velasco J, Roherty S, Srinivasiah J, Varella-Garcia M

Cancer genetics and cytogenetics. 2000 ; 122 (2) : 141-143.

PMID 11106827

A novel syndrome of radiation-associated acute myeloid leukemia involving AML1 gene translocations.

Hromas R, Shopnick R, Jumean HG, Bowers C, Varella-Garcia M, Richkind K

Blood. 2000 ; 95 (12) : 4011-4013.

PMID 10845943

A novel CBFA2 single-nucleotide mutation in familial platelet disorder with propensity to develop myeloid malignancies.

Buijs A, Poddighe P, van Wijk R, van Solinge W, Borst E, Verdonck L, Hagenbeek A, Pearson P, Lokhorst H

Blood. 2001 ; 98 (9) : 2856-2858.

PMID 11675361

Novel cryptic, complex rearrangements involving ETV6-CBFA2 (TEL-AML1) genes identified by fluorescence in situ hybridization in pediatric patients with acute lymphoblastic leukemia.

Mathew S, Shurtleff SA, Raimondi SC

Genes, chromosomes & cancer. 2001 ; 32 (2) : 188-193.

PMID 11550288

AML1-TRPS1 chimeric protein is generated by t(8;21)(q24;q22) in relapsing acute myeloblastic leukemia.

Asou N, Matsuno N, Mitsuya H

Am Soc Hematol,. 1943.

In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis.

Michaud J, Wu F, Osato M, Cottles GM, Yanagida M, Asou N, Shigesada K, Ito Y, Benson KF, Raskind WH, Rossier C, Antonarakis SE, Israels S, McNicol A, Weiss H, Horwitz M, Scott HS

Blood. 2002 ; 99 (4) : 1364-1372.

PMID 11830488

A new translocation that rearranges the AML1 gene in a patient with T-cell acute lymphoblastic leukemia.

Mikhail FM, Serry KA, Hatem N, Mourad ZI, Farawela HM, El Kaffash DM, Coignet L, Nucifora G

Cancer genetics and cytogenetics. 2002 ; 135 (1) : 96-100.

PMID 12072207

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Contributor(s)

Written	11-1997	Jean-Loup Huret
Updated	12-1997	Jean-Loup Huret
Updated	01-2003	Jean-Loup Huret and Sylvie Senon

Citation

This paper should be referenced as such :

Huret JL . AML1 (acute myeloid leukemia 1); RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)); CBFA2 (core binding factor A2). Atlas Genet Cytogenet Oncol Haematol. November 1997 . URL : http://AtlasGeneticsOncology.org/Genes/AML1.html

Huret JL . AML1 (acute myeloid leukemia 1); RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)); CBFA2 (core binding factor A2). Atlas Genet Cytogenet Oncol Haematol. December 1997 . URL : http://AtlasGeneticsOncology.org/Genes/AML1.html

Huret JL, Senon S . AML1 (acute myeloid leukemia 1); RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)); CBFA2 (core binding factor A2). Atlas Genet Cytogenet Oncol Haematol. January 2003 . URL : http://AtlasGeneticsOncology.org/Genes/AML1.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Sat Oct 11 12:48:18 2008