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t(11;14)(q24;q32) IGH/MIR125B1

Written2012-05Elise Chapiro, Florence Nguyen-Khac
Service d'Hematologie Biologique, Hopital Pitie-Salpetriere, APHP, Universite Pierre et Marie Curie-Paris 6, France

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Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id 1587

Clinics and Pathology

Disease B-cell precursor-acute lymphoblastic leukemia (BCP-ALL)
Epidemiology Rare, only 5 cases published to date (Sonoki et al., 2005; Chapiro et al., 2010; Tassano et al., 2010; Enomoto et al., 2011).
Clinics 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 BCP-ALL. 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.

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, 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.
 
  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.

Genes involved and Proteins

Gene NameIGH (Immunoglobulin Heavy)
Location 14q32.33
Gene NameMIR125B1 (microRNA 125b-1)
Location 11q24.1
Dna / Rna MicroRNAs are a family of small noncoding RNA (18-25 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 up-regulated 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).

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 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).
  

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.

Bibliography

MicroRNA miR-125b causes leukemia.
Bousquet M, Harris MH, Zhou B, Lodish HF.
Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21558-63. Epub 2010 Nov 30.
PMID 21118985
 
A new recurrent translocation t(11;14)(q24;q32) involving IGH@ and miR-125b-1 in B-cell progenitor acute lymphoblastic leukemia.
Chapiro E, Russell LJ, Struski S, Cave H, Radford-Weiss I, Valle VD, Lachenaud J, Brousset P, Bernard OA, Harrison CJ, Nguyen-Khac F.
Leukemia. 2010 Jul;24(7):1362-4. Epub 2010 May 20.
PMID 20485370
 
Eμ/miR-125b transgenic mice develop lethal B-cell malignancies.
Enomoto Y, Kitaura J, Hatakeyama K, Watanuki J, Akasaka T, Kato N, Shimanuki M, Nishimura K, Takahashi M, Taniwaki M, Haferlach C, Siebert R, Dyer MJ, Asou N, Aburatani H, Nakakuma H, Kitamura T, Sonoki T.
Leukemia. 2011 Dec;25(12):1849-56. doi: 10.1038/leu.2011.166. Epub 2011 Jul 8.
PMID 21738213
 
MicroRNAs enriched in hematopoietic stem cells differentially regulate long-term hematopoietic output.
O'Connell RM, Chaudhuri AA, Rao DS, Gibson WS, Balazs AB, Baltimore D.
Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14235-40. Epub 2010 Jul 26.
PMID 20660734
 
B-cell regulator of immunoglobulin heavy chain transcription (Bright)/ARID3a is a direct target of the oncomir microRNA-125b in progenitor B-cells.
Puissegur MP, Eichner R, Quelen C, Coyaud E, Mari B, Lebrigand K, Broccardo C, Nguyen-Khac F, Bousquet M, Brousset P.
Leukemia. 2012 Apr 3. doi: 10.1038/leu.2012.95. [Epub ahead of print]
PMID 22469780
 
MiR-125 in normal and malignant hematopoiesis.
Shaham L, Binder V, Gefen N, Borkhardt A, Izraeli S.
Leukemia. 2012 Mar 29. doi: 10.1038/leu.2012.90. [Epub ahead of print]
PMID 22456625
 
Insertion of microRNA-125b-1, a human homologue of lin-4, into a rearranged immunoglobulin heavy chain gene locus in a patient with precursor B-cell acute lymphoblastic leukemia.
Sonoki T, Iwanaga E, Mitsuya H, Asou N.
Leukemia. 2005 Nov;19(11):2009-10.
PMID 16151463
 
MicroRNA-125b-1 and BLID upregulation resulting from a novel IGH translocation in childhood B-Cell precursor acute lymphoblastic leukemia.
Tassano E, Acquila M, Tavella E, Micalizzi C, Panarello C, Morerio C.
Genes Chromosomes Cancer. 2010 Aug;49(8):682-7.
PMID 20544842
 

Citation

This paper should be referenced as such :
Chapiro, E ; Nguyen-Khac, F
t(11;14)(q24;q32) IGH/miR-125b-1
Atlas Genet Cytogenet Oncol Haematol. 2012;16(10):746-748.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t1114q24q32IGHMIR125B1ID1587.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(11;14)(q24;q32) IGH/MIR125B1

External links

IGH (14q32.33) MIR125B1 (11q24.1)

Mitelman databaset(11;14)(q24;q32) [Case List]    t(11;14)(q24;q32) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9811/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
Mitelman databaseIGH/MIR125B1 [MCList]  IGH (14q32.33) MIR125B1 (11q24.1)
 
Disease databaset(11;14)(q24;q32) IGH/MIR125B1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
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