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

1997-12-01 Jean-Loup Huret Affiliation

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

Identity

HGNC

MLLT3

LOCATION

9p21.3

IMAGE

LEGEND

AF9 (9p22) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

LOCUSID

4300

FUSION GENES

Show Gene Fusions

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

t(9;11) (p22;q23)/AML -->KMT2A -MLLT3

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)

Article Bibliography

Pubmed ID	Last Year	Title	Authors
2177642	1990	Implication 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
7542910	1995	Molecular basis of 11q23 rearrangements in hematopoietic malignant proliferations.	Bernard OA et al
8934541	1996	Identification of MLL and chimeric MLL gene products involved in 11q23 translocation and possible mechanisms of leukemogenesis by MLL truncation.	Joh T et al
8558942	1996	11q23 rearrangements in acute leukemia.	Rubnitz JE et al
8977038	1996	Chromosome 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 ID	Transcript ID	Uniprot
ENSG00000171843	ENST00000380321	B1APT5
ENSG00000171843	ENST00000380338	P42568
ENSG00000171843	ENST00000380338	A0A0S2Z448
ENSG00000171843	ENST00000629733	A0A0D9SF09
ENSG00000171843	ENST00000630269	P42568

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Transcriptional misregulation in cancer	KEGG	ko05202
Transcriptional misregulation in cancer	KEGG	hsa05202
Gene Expression	REACTOME	R-HSA-74160
RNA Polymerase II Transcription	REACTOME	R-HSA-73857
RNA Polymerase II Pre-transcription Events	REACTOME	R-HSA-674695
RNA Polymerase II Transcription Elongation	REACTOME	R-HSA-75955
Formation of RNA Pol II elongation complex	REACTOME	R-HSA-112382

Protein levels (Protein atlas)

Not detected

Low

Medium

High

PharmGKB

Entity ID	Name	Type	Evidence	Association	PD	PMIDs
PA443450	Asthma	Disease	ClinicalAnnotation	associated	PD	26083242
PA443512	Urinary Bladder Neoplasms	Disease	ClinicalAnnotation	associated	PD	27150640
PA449014	cisplatin	Chemical	ClinicalAnnotation	associated	PD	27150640
PA450546	montelukast	Chemical	ClinicalAnnotation	associated	PD	26083242

References

Pubmed ID	Year	Title	Citations
38576284	2024	Impact of MLL::AF9 Gene Rearrangement on Survival of Acute Myeloid Leukaemia Patients: An Insight into Pakistani Population.	0
38576284	2024	Impact of MLL::AF9 Gene Rearrangement on Survival of Acute Myeloid Leukaemia Patients: An Insight into Pakistani Population.	0
36358022	2023	The adverse impact of ecotropic viral integration site-1 (EVI1) overexpression on the prognosis of acute myeloid leukemia with KMT2A gene rearrangement in different risk stratification subtypes.	1
37108167	2023	Molecular Recognition of Methacryllysine and Crotonyllysine by the AF9 YEATS Domain.	0
37565737	2023	AF9 sustains glycolysis in colorectal cancer via H3K9ac-mediated PCK2 and FBP1 transcription.	1
36358022	2023	The adverse impact of ecotropic viral integration site-1 (EVI1) overexpression on the prognosis of acute myeloid leukemia with KMT2A gene rearrangement in different risk stratification subtypes.	1
37108167	2023	Molecular Recognition of Methacryllysine and Crotonyllysine by the AF9 YEATS Domain.	0
37565737	2023	AF9 sustains glycolysis in colorectal cancer via H3K9ac-mediated PCK2 and FBP1 transcription.	1
34174329	2022	The Intrinsically Disordered Proteins MLLT3 (AF9) and MLLT1 (ENL) - Multimodal Transcriptional Switches With Roles in Normal Hematopoiesis, MLL Fusion Leukemia, and Kidney Cancer.	11
34174329	2022	The Intrinsically Disordered Proteins MLLT3 (AF9) and MLLT1 (ENL) - Multimodal Transcriptional Switches With Roles in Normal Hematopoiesis, MLL Fusion Leukemia, and Kidney Cancer.	11
33221433	2021	The miR-5694/AF9/Snail Axis Provides Metastatic Advantages and a Therapeutic Target in Basal-like Breast Cancer.	8
33928666	2021	The Transcriptional Coactivator, ALL1-Fused Gene From Chromosome 9, Simultaneously Sustains Hypoxia Tolerance and Metabolic Advantages in Liver Cancer.	7
33221433	2021	The miR-5694/AF9/Snail Axis Provides Metastatic Advantages and a Therapeutic Target in Basal-like Breast Cancer.	8
33928666	2021	The Transcriptional Coactivator, ALL1-Fused Gene From Chromosome 9, Simultaneously Sustains Hypoxia Tolerance and Metabolic Advantages in Liver Cancer.	7
32954361	2020	BCOR Binding to MLL-AF9 Is Essential for Leukemia via Altered EYA1, SIX, and MYC Activity.	12

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-(myeloid-lymphoid-or-mixed-lineage-leukemia-(trithorax-homolog-drosophila);-translocated-to-3)