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t(2;11)(p21;q24) MIR125B1/?

Written2017-12Adriana Zamecnikova
Kuwait Cancer Control Center, Kuwait annaadria@yahoo.com

Abstract Review on t(2;11)(p21;q24), with data on clinics, and the genes involved.

Keywords MicroRNA, t(2;11) translocation; myeloid malignancies.

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424
ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
ICD-Morpho 9985/3 Refractory cytopenia with multilineage dysplasia; Refractory cytopenia of childhood
ICD-Morpho 9874/3 AML with maturation
ICD-Morpho 9866/3 Acute promyelocytic leukaemia with t(15;17)(q22;q12); PML-RARA
Atlas_Id 1812
 
  Figure 1. Partial karyotypes showing rearrangement between chromosomes 2 and 11 (A). Fluorescence in situ hybridization with LSI MLL (KMT2A) and LSI MYCN break-apart probes (Abott Molecular/Vysis, US) showing normal MLL signals on chromosome 11 and der(11) and translocation of MYCN located on 2p24 telomeric to MLL gene (B).

Clinics and Pathology

Disease Chronic and acute myeloid malignancies
Phenotype / cell stem origin 1 acute promyelocytic leukemia (APL) (Prigogina et al., 1986), 1 acute myeloid leukemia with maturation (AML-M2) that developed after a short period of myelodysplastic syndrome (Testoni et al., 1989), 1 refractory cytopenia with multilineage dysplasia (RCMD) (Thorsen et al., 2012) and 1 myelodysplastic/myeloproliferative neoplasm (MPN), unclassifiable (McCormick et al., 2014).
Epidemiology 3 males and 1 female aged 34, 52, 54 and 65 years.
Prognosis The patient with M2-AML reached a complete remission after chemotherapy (Testoni et al, 1989). The patient with RCMD received treatment with lenalidomide and 6 months later presented with a complete hematological and major cytogenetic response, followed by cytogenetic relapse but with no signs of transformation without therapy 3+ years from the diagnosis (Thorsen et al., 2012). Similarly, the patient with a clinically stable polycythemia vera-like myeloid neoplasm requires only periodic phlebotomies 70 months after diagnosis (McCormick et al., 2014). These data suggests that t(2:11)(p21;q24) may occur in patients with a clinically indolent myeloproliferative disorder.

Cytogenetics

Cytogenetics Morphological Because of difficulties to determine terminal 11q chromosome breakpoints and because of the similar cytogenetic appearance of translocations t(2;11)(p21;q24) and the more common t(2;11)(p21;q23) that has been described with or t(2;11)(p21;q23) without MLL ( KMT2A) involvement, FISH is recommended to exclude 11q23/MLL rearrangements.
Additional anomalies Found in association with 5q deletions in 3 out of 4 patients: in AML-M2 (Testoni et al., 1989), RCMD (Thorsen et al., 2012) and in the MPN patient (McCormick et al., 2014). The later was found to carry a mutation in exon 12 of JAK2 with two clonally-related abnormal cell lines with t(2;11)(p21;q23-24) and 11q breakpoints near a miR-125b-1 locus at 11q24. One of this clones had the t(2;11)(p21;q23-24) as a sole anomaly, the other had del(5)(q15q31) in a side-line and a third abnormal clone showed del(5q)(q13q31) as a sole abnormality, with breakpoints distinct from the t(2;11)-associated del(5q) clone. Found with +19 and non-recurring abnormalities in the APL patient (Prigogina et al., 1986).

Genes involved and Proteins

Gene NameMIR125B1 (microRNA 125b-1)
Location 11q24.1
Dna / Rna Description microRNAs (miRNAs) are short non-coding RNAs of about 19-22 nucleotides in length that play a role in post-transcriptional regulation of gene expression by affecting both the stability and translation of mRNAs. miRNAs have multiple functions including regulation of cellular proliferation, differentiation, and cell death. MIR125B1 has found to play a role in regulation of normal haematopoiesis (Thorsen et al., 2012; McCormick et al., 2014).

Result of the chromosomal anomaly

Fusion Protein
Oncogenesis The chromosomal translocation t(2;11)(p21;q24) has been described in myeloid neoplasias, suggesting its involvement in deregulation of genes relevant in myeloid cell transformation. t(2;11)(p21;q24) is accompanied by other anomalies, particularly with deletion of the long arm of chromosome 5 that is also characteristic of myeloid malignancies, therefore probably representing a secondary abnormality in these patients. The translocation breakpoint in t(2;11)(p21;q24) had been mapped close to microRNA locus, MIR125B1 at 11q24 that have been suggested to be pathogenetically involved (Bousquet et al., 2010; Thorsen et al., 2012; McCormick et al., 2014). According to these recent reports, this translocation has not been found to lead to gene fusion but is associated with deregulation of MIR125B1, supporting its pathogenetic role in oncogenesis. MIR125B1 is a regulator of normal hematopoiesis and its overexpression has been found to target several genes (STAT3, BAK1, JUN, JUND, and LIN28A) capable of modulating hematopoietic development (Bousquet et al., 2010). Dysregulated MIR125B1 may promote leukaemogenesis by arresting myeloid and monocytic differentiation, promoting stem cell renewal and targeting multiple factors in the TP53 pathway (Bousquet et al., 2010; McCormick et al., 2014). In addition to increased expression of MIR125B1 in patients with a t(2;11)(p21;q24), it is also possible and that disease pathogenesis may be influenced by other concurrent aberrations, such as 5q deletions and JAK2 mutations that may act in a concurrent or synergistic way.
Note also the existence of a t(11;14)(q24;q32) IGH/MIR125B1
  

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
PMID 21118985
 
Myeloid neoplasm with translocation t(2;11)(p21;q23-24), elevated microRNA 125b-1, and JAK2 exon 12 mutation
McCormick SR, Higgins RR, Grutkoski PS, Bousquet M, Quelen C, Bartholomaus LM, Brousset P
Br J Haematol 2015 Apr;169(2):290-3
PMID 25316507
 
Chromosomes in acute nonlymphocytic leukemia
Prigogina EL, Fleischman EW, Puchkova GP, Mayakova SA, Volkova MA, Protasova AK, Frenkel MA
Hum Genet 1986 Jun;73(2):137-46
PMID 3721500
 
5q- and t(2;11) in a patient with M2 acute non-lymphocytic leukemia
Testoni N, Zaccaria A, Celso B, Tassinari A, Rosti G, Tura S
Case report Haematologica
PMID 2628243
 
Myelodysplastic syndrome with a t(2;11)(p21;q23-24) and translocation breakpoint close to miR-125b-1
Thorsen J, Aamot HV, Roberto R, Tjønnfjord GE, Micci F, Heim S
Cancer Genet 2012 Oct;205(10):528-32
PMID 22944560
 

Citation

This paper should be referenced as such :
Zamecnikova A
t(2;11)(p21;q24) MIR125B1/?;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0211p21q24MIR125B1ID1812.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(2;11)(p21;q24) MIR125B1/?

External links

Mitelman databaset(2;11)(p21;q24) [Case List]    t(2;11)(p21;q24) [Transloc-MCList] MIR125B1/? [Fusion-MCList]
arrayMap (UZH-SIB Zurich)Morph ( 9975/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9985/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9874/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9866/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
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