MLLT3 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 3)

1997-12-01   Jean-Loup Huret 

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

Identity

HGNC
LOCATION
9p21.3
IMAGE
Atlas Image
LEGEND
AF9 (9p22) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
FUSION GENES

DNA/RNA

Transcription

5 kb mRNA; coding sequence: 1.7 kb

Proteins

Description

568 amino acids; 63 kDa; serine and proline rich in many places; possesses a nuclear targeting sequence

Localisation

nuclear

Function

transcription activator

Homology

with ENL (human)

Implicated in

Entity name
Disease
M5/M4 de novo and therapy related AML
Prognosis
the prognosis may not be as poor as in other 11q23 leukaemias in de novo cases; very poor prognosis in secondary AML cases
Cytogenetics
may be overlooked; often as a sole anomaly
Hybrid gene
variable breakpoints on both genes
Fusion 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 exemple)

Bibliography

Pubmed IDLast YearTitleAuthors
21776421990Implication of prior treatment with drug combinations including inhibitors of topoisomerase II in therapy-related monocytic leukemia with a 9;11 translocation.Albain KS et al
75429101995Molecular basis of 11q23 rearrangements in hematopoietic malignant proliferations.Bernard OA et al
89345411996Identification of MLL and chimeric MLL gene products involved in 11q23 translocation and possible mechanisms of leukemogenesis by MLL truncation.Joh T et al
8558942199611q23 rearrangements in acute leukemia.Rubnitz JE et al
89770381996Chromosome abnormalities in leukaemia: the 11q23 paradigm.Young BD et al

Other Information

Locus ID:

NCBI: 4300
MIM: 159558
HGNC: 7136
Ensembl: ENSG00000171843

Variants:

dbSNP: 4300
ClinVar: 4300
TCGA: ENSG00000171843
COSMIC: MLLT3

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000171843ENST00000380321B1APT5
ENSG00000171843ENST00000380338P42568
ENSG00000171843ENST00000380338A0A0S2Z448
ENSG00000171843ENST00000629733A0A0D9SF09
ENSG00000171843ENST00000630269P42568

Expression (GTEx)

0
5
10
15
20
25

Pathways

PathwaySourceExternal ID
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202
Gene ExpressionREACTOMER-HSA-74160
RNA Polymerase II TranscriptionREACTOMER-HSA-73857
RNA Polymerase II Pre-transcription EventsREACTOMER-HSA-674695
RNA Polymerase II Transcription ElongationREACTOMER-HSA-75955
Formation of RNA Pol II elongation complexREACTOMER-HSA-112382

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA443450AsthmaDiseaseClinicalAnnotationassociatedPD26083242
PA443512Urinary Bladder NeoplasmsDiseaseClinicalAnnotationassociatedPD27150640
PA449014cisplatinChemicalClinicalAnnotationassociatedPD27150640
PA450546montelukastChemicalClinicalAnnotationassociatedPD26083242

References

Pubmed IDYearTitleCitations
185387322008Microenvironment determines lineage fate in a human model of MLL-AF9 leukemia.137
254171072014AF9 YEATS domain links histone acetylation to DOT1L-mediated H3K79 methylation.103
271051142016Molecular Coupling of Histone Crotonylation and Active Transcription by AF9 YEATS Domain.77
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
273449462016MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome.59
232606552013Leukemia fusion target AF9 is an intrinsically disordered transcriptional regulator that recruits multiple partners via coupled folding and binding.34
175818652007Oncogenic All1 fusion proteins target Drosha-mediated microRNA processing.31
231787542013MLL-AF9-mediated immortalization of human hematopoietic cells along different lineages changes during ontogeny.24
198644292009AF17 competes with AF9 for binding to Dot1a to up-regulate transcription of epithelial Na+ channel alpha.23
206898072010Genetic variation and antioxidant response gene expression in the bronchial airway epithelium of smokers at risk for lung cancer.23

Citation

Jean-Loup Huret

MLLT3 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 3)

Atlas Genet Cytogenet Oncol Haematol. 1997-12-01

Online version: http://atlasgeneticsoncology.org/gene/5/mllt3