TLX3 (T-cell leukemia, homeobox protein 3)

2004-03-01   Roderick AF MacLeod , Stefan Nagel 

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

Identity

HGNC
LOCATION
5q35.1
IMAGE
Atlas 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
ALIAS
HOX11L2,RNX
FUSION GENES

DNA/RNA

Atlas Image

Description

3 exons on 2.23 kb

Transcription

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

Proteins

Atlas Image

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
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

Atlas Image
Atlas Image

Note

Within the upstream region or within the neighboring gene RanBP17.

Bibliography

Pubmed IDLast YearTitleAuthors
121305132002HOX11L2 expression defines a clinical subtype of pediatric T-ALL associated with poor prognosis.Ballerini P et al
129707862003t(5;14)/HOX11L2-positive T-cell acute lymphoblastic leukemia. A collaborative study of the Groupe Français de Cytogénétique Hématologique (GFCH).Berger R et al
115872052001A 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
145041102004Clinical 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
114357162001Assignment 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
120868902002Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia.Ferrando AA et al
123999632002Disruption 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
114357182001Assignment of the human homeobox 11-like 2 gene (HOX11L2) to chromosome 5q34-->q35 by radiation hybrid mapping.Lee-Kirsch MA et al
126610092003Activation 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
124547472002High incidence of Hox11L2 expression in children with T-ALL.Mauvieux L et al
145003642003The 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 IDTranscript IDUniprot
ENSG00000164438ENST00000296921O43711

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45
50

Pathways

PathwaySourceExternal ID
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
223669492012Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL.61
225162632012TLX homeodomain oncogenes mediate T cell maturation arrest in T-ALL via interaction with ETS1 and suppression of TCRα gene expression.36
213747612011Wnt signaling promotes neuronal differentiation from mesenchymal stem cells through activation of Tlx3.34
173080842007Activation of TLX3 and NKX2-5 in t(5;14)(q35;q32) T-cell acute lymphoblastic leukemia by remote 3'-BCL11B enhancers and coregulation by PU.1 and HMGA1.28
152408572004Sudden infant death syndrome: case-control frequency differences at genes pertinent to early autonomic nervous system embryologic development.17
145041102004Clinical 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 58951.15
129707862003t(5;14)/HOX11L2-positive T-cell acute lymphoblastic leukemia. A collaborative study of the Groupe Français de Cytogénétique Hématologique (GFCH).12
181855242008Cooperative genetic defects in TLX3 rearranged pediatric T-ALL.11
121305132002HOX11L2 expression defines a clinical subtype of pediatric T-ALL associated with poor prognosis.10
216178532011Aberrant DNA methylation of T-cell leukemia, homeobox 3 modulates cisplatin sensitivity in bladder cancer.8

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/tlx3id398