Download Leukaemia Section t(7;19)(q34;p13) Atlas of Genetics and Cytogenetics in Oncology and Haematology

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
OPEN ACCESS JOURNAL AT INIST-CNRS
Leukaemia Section
Mini Review
t(7;19)(q34;p13)
Jacques Boyer
Laboratoire d'Hématologie, CH du MANS, France (JB)
Published in Atlas Database: January 2003
Online updated version: http://AtlasGeneticsOncology.org/Anomalies/t0719q34p13ID1060.html
DOI: 10.4267/2042/37960
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2003 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Prognosis
Identity
HOX11 activation is significantly associated with a
favorable prognosis, while expression of TAL1, LYL1
and surprisingly HOX11L2 confers a much worse
response to treatment.
The upregulation of BCL2 may explain their relative
resistance to chemotherapy.
Note
Non random translocations involving the short arm of
chromosome 19 are observed in acute leukemia. The
19p13 genes E2A and LYL1 (see below) lie at two
different
translocation
breakpoints
in
acute
lymphoblastic leukemia.
For instance the E2A gene is involved in the
t(1;19)(q23 ;p13) in acute pre-B leukemia (B-ALL) and
the LYL1 gene is structurally altered in the t(7;19)(q34
;p13) in T cell leukemia (T-ALL).
Cytogenetics
Cytogenetics morphological
19p13 is a partner of 7q34. The other partners are 1p34,
1p32, 9q34,9q32,10q24,11p13, 15q22.
Clinics and pathology
Genes involved and proteins
Disease
TCRB (T-cell receptor beta-chain gene)
Specifically associated with T-cell Acute lymphoblastic
leukemia (T-ALL).
Location
7q35
DNA/RNA
The TRB locus at 7q35 spans 685 Kb. The locus
contains 2 types of coding elements : TCR elements
(64-67 variable genes TRBV, 2 clusters of diversity,
joining and constant segments) and 8 trypsinogen
genes.
Protein
T cell receptor beta chains.
Phenotype/cell stem origin
Recents works, using oligonucleotide microarrays,
show that several gene expression signatures are
indicative of leukemic arrest at specific stages of
normal thymocyte development:
LYL1 signature: pro-T (CD34+ CD3- CD4- CD8CD1a-).
HOX11: early cortical thymocyte and TAL1 late
cortical thymocyte.
LYL1 positivity is related to higher expression levels of
the MYCN, LMO2 and PLZF proto-oncogenes as well
as the antiapoptotic gene BCL2.
These findings have clinical importance (see
Prognosis).
LYL1
Location
19p13.2-p13.1
Note
The LYL1 gene is assigned to 19p13.2-p13.1 by
fluorescence in situ hybridation.
Epidemiology
Rare: < 1% among T-ALL. The t(7;9)(q34;q32) is
present in one case of a serie of 5 patients with 7q34
involvment.
Atlas Genet Cytogenet Oncol Haematol. 2003; 7(2)
107
t(7;19)(q34;p13)
Boyer J
Ectopic expression of LYL1 cause a significant
decrease in NF-KappaB- dependant transcription
associated with a reduced level of NF-KappaBdependant proteins.
DNA/RNA
An RNA of about 1.5 kb is transcribed from this gene
in a wide variety of lymphoid cell lines with the notable
exception of thymocytes and T cells.
Protein
LYL1 encodes a basic helix-loop-helix (bHLH)
phosphoprotein (size 108 amino acids) that is highly.
Related to TAL1: TAL1 and LYL1 HLH proteins show
an 87% level of aminoacid identity.
References
Smith SD, Morgan R, Gemmell R, Amylon MD, Link MP, Linker
C, Hecht BK, Warnke R, Glader BE, Hecht F. Clinical and
biologic
characterization
of
T-cell
neoplasias
with
rearrangements of chromosome 7 band q34. Blood. 1988
Feb;71(2):395-402
Result of the chromosomal
anomaly
Mellentin JD, Smith SD, Cleary ML. lyl-1, a novel gene altered
by chromosomal translocation in T cell leukemia, codes for a
protein with a helix-loop-helix DNA binding motif. Cell. 1989 Jul
14;58(1):77-83
Hybrid gene
Description
The LYL1 gene is structurally altered following the
t(7;19) translocation, resulting in its head-to-head
juxtaposition with the T cell receptor beta gene.
In the human T cell line SUP-T7 established from an
acute lymphoblastic leukemia, nucleotide sequence
analysis showed that the point of crossover on
chromosome 7 occured immediately adjacent to joining
segment beta 1.1 within the TCR beta gene, suggesting
that this translocation resulted from an error in TCR
gene rearrangement.
The t(7;19) resulted in truncation of the LYL1 gene and
production of abnormal-sized RNAs suggesting a role
for LYL1 in the pathogenesis of T Leukemia.
Secker-Walker LM, Campana D, Hawkins JM, Sampson RE,
Coustan-Smith E. Karyotype and T-cell receptor expression in
T-lineage acute lymphoblastic leukemia. Genes Chromosomes
Cancer. 1992 Jan;4(1):41-5
Fusion protein
Miyamoto A, Cui X, Naumovski L, Cleary ML. Helix-loop-helix
proteins LYL1 and E2a form heterodimeric complexes with
distinctive DNA-binding properties in hematolymphoid cells.
Mol Cell Biol. 1996 May;16(5):2394-401
Baer R. TAL1, TAL2 and LYL1: a family of basic helix-loophelix proteins implicated in T cell acute leukaemia. Semin
Cancer Biol. 1993 Dec;4(6):341-7
Trask B, Fertitta A, Christensen M, Youngblom J, Bergmann A,
Copeland A, de Jong P, Mohrenweiser H, Olsen A, Carrano A.
Fluorescence in situ hybridization mapping of human
chromosome 19: cytogenetic band location of 540 cosmids and
70 genes or DNA markers. Genomics. 1993 Jan;15(1):133-45
. Cytogenetic abnormalities in adult acute lymphoblastic
leukemia: correlations with hematologic findings outcome. A
Collaborative Study of the Group Français de Cytogénétique
Hématologique. Blood. 1996 Apr 15;87(8):3135-42
Oncogenesis
Several helix-loop-helix (HLH) proteins are proposed
to function as transcriptionnal regulatory factors based
on their ability to bind in vitro the E-box motif of
transcriptional enhancers. The enhancer binding HLH
proteins include E47 and E12, two distinct but related
polypeptides encoded by E2A gene that are able to
form heterologous complexes with other HLH proteins
like TAL1 and LYL1 polypeptides.
Thus LYL1 may function as a dominant-negative
mutant preventing the activation of E2A responsive
genes. It is plausible that the inactivation of E2A target
genes is an essential and common step toward the
development of a number of T-cell malignancies.
LYL1 interacts also with p105 the precursor of NFKappaB1 p50. Biochemical studies indicate that this
interaction is mediated by the HLH motif of LYL1 and
the ankyrin-like motifs of p105.
Atlas Genet Cytogenet Oncol Haematol. 2003; 7(2)
Bain G, Engel I, Robanus Maandag EC, te Riele HP, Voland
JR, Sharp LL, Chun J, Huey B, Pinkel D, Murre C. E2A
deficiency leads to abnormalities in alphabeta T-cell
development and to rapid development of T-cell lymphomas.
Mol Cell Biol. 1997 Aug;17(8):4782-91
Ferrier R, Nougarede R, Doucet S, Kahn-Perles B, Imbert J,
Mathieu-Mahul D. Physical interaction of the bHLH LYL1
protein and NF-kappaB1 p105. Oncogene. 1999 Jan
28;18(4):995-1005
Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C,
Raimondi SC, Behm FG, Pui CH, Downing JR, Gilliland DG,
Lander ES, Golub TR, Look AT. Gene expression signatures
define novel oncogenic pathways in T cell acute lymphoblastic
leukemia. Cancer Cell. 2002 Feb;1(1):75-87
This article should be referenced as such:
Boyer J. t(7;19)(q34;p13). Atlas Genet Cytogenet Oncol
Haematol. 2003; 7(2):107-108.
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