TLX3 (T-cell leukemia, homeobox protein 3)

2004-03-01 Roderick AF MacLeod , Stefan Nagel Affiliation

DSMZ-Deutsche Sammlung von, Mikroorganismen und Zellkulturen, Inhoffenstr. 7B, D-38124 Braunschweig, Germany

Identity

HGNC

TLX3

LOCATION

5q35.1

IMAGE

LEGEND

TLX3 (5q35.1): FISH with BAC clone ctb-45L16 (red) showing a breakpoint signal in the consensus breakpoint region split between der(5) and der(14) partners. Analysis was performed on the pediatric T-ALL cell line HPB-ALL (DSMZ ACC-483) which carries t(5;14)(q35.1;q32.2) as part of a complex 4-way rearrangement involving chromosomes 1 and 16. Normally (in the absence of secondary translocations) the breakpoints on both partners lie closely equidistant to the q-arm telomeres rendering the translocation cryptic and difficult to detect even with chromosome painting.

LOCUSID

30012

ALIAS

HOX11L2,RNX

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

3 exons on 2.23 kb

Transcription

In a centromeric --> telomeric orientation; 876 bp mRNA (coding)

Proteins

Description

291 amino acids, 31.8 kDa; contains one homeobox domain (residues 166-221)

Expression

Narrowly restricted to brain.

Localisation

Probably nuclear

Function

Murine Tlx-3 and Tlx-1 together sustain expression of Drg-11, and control development of somatic and visceral relay sensory neurons.

Homology

With homeobox genes, especially with those of the NK-like family.

Implicated in

Entity name

t(5;14)(q35;q32) in T-ALL-->TLX3 - BCL11B

Disease

T-cell acute lymphocytic leukemia (T-ALL)

Prognosis

TLX3 expression may denote poor prognosis.

Cytogenetics

Cryptic translocation detectable by locus specific FISH. t(5;14) may exclude del(1)(p32) SIL-TAL1 fusion.

Hybrid gene

5 TLX3-3 BCL11B on der(14).

Oncogenesis

Ectopic expression in T-cells

Entity name

t(5;14)(q35;q11) in T-ALL --> TLX3 - TCRD

Disease

T-cell acute lymphocytic leukemia (T-ALL)

Cytogenetics

Apparent variant of t(5;14)

Hybrid gene

5 TLX3-TCRD on der(14)

Breakpoints

Note

Within the upstream region or within the neighboring gene RanBP17.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
12130513	2002	HOX11L2 expression defines a clinical subtype of pediatric T-ALL associated with poor prognosis.	Ballerini P et al
12970786	2003	t(5;14)/HOX11L2-positive T-cell acute lymphoblastic leukemia. A collaborative study of the Groupe Français de Cytogénétique Hématologique (GFCH).	Berger R et al
11587205	2001	A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia.	Bernard OA et al
14504110	2004	Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951.	Cavé H et al
11435716	2001	Assignment of the HOX11L2 gene to human chromosome band 5q35.1 and of its murine homolog to mouse chromosome bands 11A4-A5 by in situ hybridization.	Cinti R et al
12086890	2002	Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia.	Ferrando AA et al
12399963	2002	Disruption of the RanBP17/Hox11L2 region by recombination with the TCRdelta locus in acute lymphoblastic leukemias with t(5;14)(q34;q11).	Hansen-Hagge TE et al
11435718	2001	Assignment of the human homeobox 11-like 2 gene (HOX11L2) to chromosome 5q34-->q35 by radiation hybrid mapping.	Lee-Kirsch MA et al
12661009	2003	Activation of HOX11L2 by juxtaposition with 3'-BCL11B in an acute lymphoblastic leukemia cell line (HPB-ALL) with t(5;14)(q35;q32.2).	MacLeod RA et al
12454747	2002	High incidence of Hox11L2 expression in children with T-ALL.	Mauvieux L et al
14500364	2003	The cardiac homeobox gene NKX2-5 is deregulated by juxtaposition with BCL11B in pediatric T-ALL cell lines via a novel t(5;14)(q35.1;q32.2).	Nagel S et al

Other Information

Locus ID:

NCBI: 30012
MIM: 604640
HGNC: 13532
Ensembl: ENSG00000164438

Variants:

dbSNP: 30012
ClinVar: 30012
TCGA: ENSG00000164438
COSMIC: TLX3

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000164438	ENST00000296921	O43711

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

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
24571118	2016	NKX2-5, SIL/TAL and TLX3/HOX11L2 expression in Egyptian pediatric T-cell acute lymphoblastic leukemia.	2
26852660	2016	Immunophenotyping with CD135 and CD117 predicts the FLT3, IL-7R and TLX3 gene mutations in childhood T-cell acute leukemia.	3
24571118	2016	NKX2-5, SIL/TAL and TLX3/HOX11L2 expression in Egyptian pediatric T-cell acute lymphoblastic leukemia.	2
26852660	2016	Immunophenotyping with CD135 and CD117 predicts the FLT3, IL-7R and TLX3 gene mutations in childhood T-cell acute leukemia.	3
24997618	2015	AMBRA1 and BECLIN 1 interplay in the crosstalk between autophagy and cell proliferation.	0
24997618	2015	AMBRA1 and BECLIN 1 interplay in the crosstalk between autophagy and cell proliferation.	0
22366949	2012	Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL.	80
22516263	2012	TLX homeodomain oncogenes mediate T cell maturation arrest in T-ALL via interaction with ETS1 and suppression of TCRα gene expression.	50
22366949	2012	Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL.	80
22516263	2012	TLX homeodomain oncogenes mediate T cell maturation arrest in T-ALL via interaction with ETS1 and suppression of TCRα gene expression.	50
21225930	2011	Successful treatment of a child with T/myeloid acute bilineal leukemia associated with TLX3/BCL11B fusion and 9q deletion.	9
21374761	2011	Wnt signaling promotes neuronal differentiation from mesenchymal stem cells through activation of Tlx3.	44
21617853	2011	Aberrant DNA methylation of T-cell leukemia, homeobox 3 modulates cisplatin sensitivity in bladder cancer.	12
21225930	2011	Successful treatment of a child with T/myeloid acute bilineal leukemia associated with TLX3/BCL11B fusion and 9q deletion.	9
21374761	2011	Wnt signaling promotes neuronal differentiation from mesenchymal stem cells through activation of Tlx3.	44

Citation

Roderick AF MacLeod ; Stefan Nagel

TLX3 (T-cell leukemia, homeobox protein 3)

Atlas Genet Cytogenet Oncol Haematol. 2004-03-01

Online version: http://atlasgeneticsoncology.org/gene/398/deep-insight-explorer/teaching-explorer/gene-fusions/?id=398