Download Leukaemia Section t(11;14)(q24;q32) IGH/miR -125b-1 Atlas of Genetics and Cytogenetics

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Leukaemia Section
Short Communication
t(11;14)(q24;q32) IGH/miR-125b-1
Elise Chapiro, Florence Nguyen-Khac
Service d'Hematologie Biologique, Hopital Pitie-Salpetriere, APHP, Universite Pierre et Marie Curie-Paris 6,
France (EC, FNK)
Published in Atlas Database: May 2012
Online updated version : http://AtlasGeneticsOncology.org/Anomalies/t1114q24q32IGHMIR125B1ID1587.html
DOI: 10.4267/2042/48153
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology
associated with a t(1;3)(p?33;q2?7) and +21. In the
other one, the t(11;14) was associated with a
del(9)(p13) and dic(?13;15)(q?;q10). In the pediatric
case reported by Tassano et al., the t(11;14) was the
sole abnormality.
Clinics and pathology
Disease
B-cell precursor-acute lymphoblastic leukemia (BCPALL)
Epidemiology
Genes involved and proteins
Rare, only 5 cases published to date (Sonoki et al.,
2005; Chapiro et al., 2010; Tassano et al., 2010;
Enomoto et al., 2011).
IGH@
Location
14q32
Clinics
miR-125b-1
Sonoki et al. reported a 35-year-old woman with a
leukemic recurrence as bilateral ovarian tumors 7 years
after allogenic bone marrow transplantation for BCPALL.
Chapiro et al. reported two further adult cases: a female
patient aged 45 years with an early-pre-B phenotype
who died 21 months after diagnostic, and a male patient
aged 33 years who were alive 4 months after diagnosis.
Tassano et al. described a 12-year-old girl who
developed a dramatic macrophage activation and died
during the induction phase of treatment.
Location
11q24
DNA/RNA
MicroRNAs are a family of small noncoding RNA (1825 nucleotides) that play a key role in many
fundamental processes, including differentiation,
proliferation, and apoptosis, by regulating gene
expression at the posttranscriptional level. MicroRNA
miR-125b is the ortholog of lin-4 in Caenorhaditis
elegans.
It is transcribed from two loci located on chromosomes
11q24 (miR-125b-1) and 21q21 (miR-125b-2).
Mir-125b is involved in hematopoiesis: it enhances
survival and proliferation of early hematopoietic
progenitors and blocks their terminal differentiation
(Shaham et al., 2012).
Mir-125b-1 and miR-125b-2 are both reported to be upregulated in some solid cancers and hematological
malignancies, including BCP-ALL, and AML/MDS.
In the latter, the over-expression of miR-125b-1 is the
result of the rare translocation t(2;11)(p21;q23)
(Bousquet et al., 2008).
Cytogenetics
Note
In the case reported by Sonoki et al., the t(11;14) was
not detected by cytogenetic analyses: an insertion of
miR-125b-1 sequence into the IGH locus was found by
molecular analyses.
Cytogenetics morphological
In one of the cases described by Chapiro et al., only the
derivated chromosome 14 of t(11;14) was present,
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(10)
746
t(11;14)(q24;q32) IGH/miR-125b-1
Chapiro E, Nguyen-Khac F
Metaphase chromosomes hybridized with clones RP11-419A21 (Spectrum green) and RP11-164B14 (Spectrum red). A red/green fusion
signal is seen on the normal chromosome 11, a red signal is relocated to the der(14) while a green signal remains on the der(11).
Courtesy L Russell.
myeloproliferative neoplasms, B- and T-ALL
(Bousquet et al., 2010; O'Connell et al., 2010).
Transgenic mice mimicking the t(11;14)(Eµ/miR-125b)
die from B-cell malignancies resistant to apoptosis
(Enomoto et al., 2011). A recent study showed that
miR-125b exerts its oncogenic function in progenitor
B-cells by targeting ARID3a/Bright, a transcription
factor implicated in the regulation of expression of the
immunoglobulin heavy chain: miR-125b mediates
ARID3a repression, thus leading to a blockage in
differentiation, increased proliferation and inhibition of
apoptosis (Puissegur et al., 2012).
Result of the chromosomal
anomaly
Hybrid gene
Description
The translocation links sequences located 5 to 18 kb
centromeric of miR-125b-1 on chromosome 11 to a JH
segment on chromosome 14.
Fusion protein
Description
No fusion protein.
Oncogenesis
Transcriptional activation of miR-125b-1. Several
murine models have been described, demonstrating that
miR-125b is a leukemogenic oncogene. In bone
marrow transplantation models, mice develop fatal
hematological
malignancies
consisting
of
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(10)
References
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t(11;14)(q24;q32) IGH/miR-125b-1
Chapiro E, Nguyen-Khac F
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A
new
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This article should be referenced as such:
Chapiro E, Nguyen-Khac F. t(11;14)(q24;q32) IGH/miR-125b1. Atlas Genet Cytogenet Oncol Haematol. 2012; 16(10):746748.
Tassano E, Acquila M, Tavella E, Micalizzi C, Panarello C,
Morerio C. MicroRNA-125b-1 and BLID upregulation resulting
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(10)
748