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t(11;14)(p15;q11) TRD/LMO1

Written2002-08Jacques Boyer
Laboratoire d' hématologie, CH du MANS, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
Atlas_Id 1069

Clinics and Pathology

Disease T-cell Acute lymphoblastic leukemia T-ALL
Phenotype / cell stem origin Apparently, this translocation is not restricted to a single maturational stage. Among five cases reported in the litterature: 2 of 4 cases tested coexpressed CD4 and CD8 antigens and 2 cases showed a more immature phenotype like Pro T-ALL: cytCD3+ CD3- CD4- CD8- CD34+
Epidemiology The t(11 ;14)(p15 ;q11) occurs in less than 1% of patients with T-cell ALL
Cytology There is limited knowledge about the clinical and biologic characteristics of patients in whom this translocation is present, all of them have childhood T-cell ALL In contrast to cases with the t(11 ;14)(p13 ;q11) only one patient had a markedly elevated leucocyte count at diagnosis.
Prognosis Remarkably, no patient with this translocation has sustained durable remission.

Cytogenetics

Cytogenetics Morphological This translocation is not to be confused with the t(11 ;14)(p13 ;q11).
Additional anomalies del(6q), i(17)(q10)

Genes involved and Proteins

Gene Name LMO1
Location 11p15
Dna / Rna 1214 bp.This gene belongs to the Rhombotin family: RBTN1, RBTN2, RBTN3. Complete characterisation of these genes in man and mouse shows that all three encode cysteine-rich proteins with typical LIM domains. The exon organisation of RBTN1 and RBTN3 are similar, both having an intron, absent from the RBTN2 gene, in the LIM2 encoding region.
Protein RBTN1 and RBTN3 derivated proteins have 98% identity in the LIM domain; LMO1derivated protein is a 46kd nuclear protein. Comparison of the sequence of the human and mouse protein LMO1 shows that the main conserved sequence is a tandemly duplicated cystein-rich-region called LIM domain. LIM domain might facilitate protein-protein interaction which modulate transcription via intermolecular competitive binding between LIM domain and certain DNA-binding-transcription factors. The LDB1/NLI is a phosphoprotein and binds to LMO1 in its phophorylated state and essentially all the LMO1 and LDB1 protein in the T cell is part of the complexe. The stem cell leukemia ( SCL) transcription factor is also a partner for LMO1 and LMO2 proteins. RBTN1 and RBTN3 proteins have the same expression pattern in mouse development, since both genes show high expression in the brain, but little lymphoid expression. RBTN2 expression is more ubiquitous.
Gene Name TRA
Location 14q11.2
Dna / Rna The size of TCR alpha/delta locus is about 1 Mb. The TCR delta variable (V) diversity (D) joining (J) and constant region genes are situated within the TCR alpha locus between the TCR alpha V and the TCR alpha J segments. The TCR delta locus contains three D segments and four J segments, whereas the TCR alpha J regions spans approximately 80 Kb and contains at least 61 segments. The TCR alpha/delta locus is transcribed in a centromer to telomer direction.
Protein T-cell receptor
Gene Name TRD
Location 14q11.2
Dna / Rna The size of TCR alpha/delta locus is about 1 Mb. The TCR delta variable (V) diversity (D) joining (J) and constant region genes are situated within the TCR alpha locus between the TCR alpha V and the TCR alpha J segments. The TCR delta locus contains three D segments and four J segments, whereas the TCR alpha J regions spans approximately 80 Kb and contains at least 61 segments. The TCR alpha/delta locus is transcribed in a centromer to telomer direction.
Protein T-cell receptor

Result of the chromosomal anomaly

Hybrid gene
Description The translocation t(11 ;14)(p15 ;q11) occurs at a T-cell receptor joining J delta segment, 12 kb upstream of the constant C delta gene and 98 kb upstream of the C alpha gene at chromosome band 11q11. Rhombotin gene contains oligomers that span the breakpoint region. This breakpoint region possesses a consensus heptamer : it appers to function as a 23-signal and to synapse with a 12-signal on chromosome 14 in the translocation t(11 ;14)(p15 ;q11) but the recombinaison frequency is 20-fold lower than LMO2 and about 530-fold lower than for a normal 23-signal. The 23-signal is a part, as well as the 12-signal, of the RAG complex whose normal function is to initiate the breaks of V(D)J recombinaison.
  
Fusion Protein
Description No fusion protein.
Oncogenesis Erroneous V(D)J joining process and alteration of the transcription networks.
  

Bibliography

Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings outcome. A Collaborative Study of the Groupe Français de Cytogénétique Hématologique (GFCH).
Blood. 1996 ; 87 (8) : 3135-3142.
PMID 8605327
 
The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor C delta locus on human chromosome 14q11 and a transcribed region of chromosome 11p15.
Boehm T, Baer R, Lavenir I, Forster A, Waters JJ, Nacheva E, Rabbitts TH
The EMBO journal. 1988 ; 7 (2) : 385-394.
PMID 3259177
 
The rhombotin gene belongs to a class of transcriptional regulators with a potential novel protein dimerisation motif.
Boehm T, Foroni L, Kennedy M, Rabbitts TH
Oncogene. 1990 ; 5 (7) : 1103-1105.
PMID 2115645
 
scid Thymocytes with TCRbeta gene rearrangements are targets for the oncogenic effect of SCL and LMO1 transgenes.
Chervinsky DS, Lam DH, Melman MP, Gross KW, Aplan PD
Cancer research. 2001 ; 61 (17) : 6382-6387.
PMID 11522630
 
Pediatric leukemia/lymphoma with t(8;14)(q24;q11).
Lange BJ, Raimondi SC, Heerema N, Nowell PC, Minowada J, Steinherz PE, Arenson EB, O'Connor R, Santoli D
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1992 ; 6 (7) : 613-618.
PMID 1385638
 
T-cell receptor alpha-chain gene is split in a human T-cell leukemia cell line with a t(11;14)(p15;q11).
Le Beau MM, McKeithan TW, Shima EA, Goldman-Leikin RE, Chan SJ, Bell GI, Rowley JD, Diaz MO
Proceedings of the National Academy of Sciences of the United States of America. 1986 ; 83 (24) : 9744-9748.
PMID 3540949
 
Molecular cloning of a DNA fragment from human chromosome 14(14q11) involved in T-cell malignancies.
Mathieu-Mahul D, Caubet JF, Bernheim A, Mauchauffé M, Palmer E, Berger R, Larsen CJ
The EMBO journal. 1985 ; 4 (13A) : 3427-3433.
PMID 3912169
 
The t(11;14)(p15;q11) in a T-cell acute lymphoblastic leukemia cell line activates multiple transcripts, including Ttg-1, a gene encoding a potential zinc finger protein.
McGuire EA, Hockett RD, Pollock KM, Bartholdi MF, O'Brien SJ, Korsmeyer SJ
Molecular and cellular biology. 1989 ; 9 (5) : 2124-2132.
PMID 2501659
 
T-cell acute lymphoblastic leukemia with t(11;14) in children.
Ribeiro RC, Raimondi SC, Behm FG, Pui CH
Leukemia & lymphoma. 1992 ; 7 (5-6) : 351-358.
PMID 1493436
 
LIM domain proteins in leukaemia and development.
Sá I, Rabbitts TH
Seminars in cancer biology. 1993 ; 4 (6) : 349-358.
PMID 8142620
 
Karyotype and T-cell receptor expression in T-lineage acute lymphoblastic leukemia.
Secker-Walker LM, Campana D, Hawkins JM, Sampson RE, Coustan-Smith E
Genes, chromosomes & cancer. 1992 ; 4 (1) : 41-45.
PMID 1377008
 
CD7+, CD4-/CD8- acute leukemia with t(11;14)(p15;q11) in a child.
Silva ML, de Oliveira MS, Valente AN, Abdelhay E, Bouzas LF, Laun L, Ribeiro RC
Cancer genetics and cytogenetics. 1991 ; 56 (2) : 171-176.
PMID 1721862
 
The LMO1 and LDB1 proteins interact in human T cell acute leukaemia with the chromosomal translocation t(11;14)(p15;q11).
Valge-Archer V, Forster A, Rabbitts TH
Oncogene. 1998 ; 17 (24) : 3199-3202.
PMID 9872335
 
Translocation 11;14 in three children with acute lymphoblastic leukemia of T-cell origin.
Zalcberg IQ, Silva ML, Abdelhay E, Tabak DG, Ornellas MH, Simáes FV, Pucheri W, Ribeiro R, Seuánez HN
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PMID 7497440
 

Citation

This paper should be referenced as such :
Boyer, J
t(11;14)(p15;q11)
Atlas Genet Cytogenet Oncol Haematol. 2003;7(1):28-30.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t1114p15q11ID1069.html


Other genes implicated (Data extracted from papers in the Atlas) [ 2 ]

Genes LMO1 TRD

Translocations implicated (Data extracted from papers in the Atlas)

 t(11;14)(p15;q11) TRD/LMO1

External links

TRD (-) LMO1 (11p15.4)

Mitelman databaset(11;14)(p15;q11) [Case List]    t(11;14)(p15;q11) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9837/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
Mitelman databaseTRD/LMO1 [MCList]  TRD (-) LMO1 (11p15.4)
 
Disease databaset(11;14)(p15;q11) TRD/LMO1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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