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

2012-05-01   Florence Nguyen-Khac , Elise Chapiro 

1.Service d Hematologie Biologique, Hopital Pitie-Salpetriere, APHP, Universite Pierre et Marie Curie-Paris 6, France
2.Service dHematologie Biologique, Hopital Pitie-Salpetriere, APHP, Universite Pierre et Marie Curie-Paris 6, France

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.
Atlas Image
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 name
IGH (Immunoglobulin Heavy)
Location
14q32.33
Gene name
MIR125B1 (microRNA 125b-1)
Location
11q24.1
Dna rna description
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

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.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; OConnell 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).

Bibliography

Pubmed IDLast YearTitleAuthors
211189852010MicroRNA miR-125b causes leukemia.Bousquet M et al
204853702010A new recurrent translocation t(11;14)(q24;q32) involving IGH@ and miR-125b-1 in B-cell progenitor acute lymphoblastic leukemia.Chapiro E et al
217382132011Eμ/miR-125b transgenic mice develop lethal B-cell malignancies.Enomoto Y et al
206607342010MicroRNAs enriched in hematopoietic stem cells differentially regulate long-term hematopoietic output.O'Connell RM et al
224697802012B-cell regulator of immunoglobulin heavy-chain transcription (Bright)/ARID3a is a direct target of the oncomir microRNA-125b in progenitor B-cells.Puissegur MP et al
224566252012MiR-125 in normal and malignant hematopoiesis.Shaham L et al
161514632005Insertion 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 et al
205448422010MicroRNA-125b-1 and BLID upregulation resulting from a novel IGH translocation in childhood B-Cell precursor acute lymphoblastic leukemia.Tassano E et al

Summary

Fusion gene

IGH/MIR125B1 IGH (14q32.33) MIR125B1 (11q24.1) M t(11;14)(q24;q32)

Citation

Florence Nguyen-Khac ; Elise Chapiro

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

Atlas Genet Cytogenet Oncol Haematol. 2012-05-01

Online version: http://atlasgeneticsoncology.org/haematological/1587/t(11;14)(q24;q32)

External Links