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t(11;21)(q13;q22)

Clinics and Pathology

Disease Myeloid malignancies
Epidemiology Three cases of t(11;21)(q13;q22) in myeloid malignancies are available to date: a 63-year-old female patient with AML evolving from myelodysplastic syndrome (MDS) (Imagama et al., 2007), a 65-year-old male patient with a M2 acute myeloid leukemia (M2-AML) (Dai et al., 2007), and a 70-year-old male patient with a chronic myelogenous leukemia (CML). The t(11;21) was found during transformation into blastic crisis (BC-CML) and in the subsequent reversion to the chronic phase (Wang et al., 1988).
Prognosis The MDS-to-AML case relapsed two years after remission. The M2-AML case died 10 months after diagnosis. The CML case was remaining in remission of blast crisis for 4 months at the time of the report.

Cytogenetics

Cytogenetics Morphological The t(11;21) was part of a complex karyotype in the MDS-to-AML case, found with an additional anomaly in the M2-AML case, and accompanying the classical t(9;22)(q34;q11) in the CML case.

Genes involved and Proteins

Note The involvement of RUNX1 was proved in the two AML cases; the involvement of MACROD1/LRP16 as the partner of RUNX1 was established in the case described by Imagama et al.
Gene Name MACROD1
Location 11q13.1
Note MACROD1 is also known as LRP16
Protein MACROD1/LRP16 gene has been characterized as an estrogen-responsive gene. LRP16 is required for ERalpha signaling transduction by functioning as an ERalpha coactivator (Han et al., 2007; Han et al., 2008). MACROD1/LRP16-overexpression promotes the cell cycle, and cell proliferation (Yang et al., 2009).
Gene Name RUNX1
Location 21q22
Dna / Rna Transcription from telomere to centromere.
Protein Contains the RUNT binding domain at 5' portion and the transactivation domain at 3' portion. Forms heterodimers; widely expressed; nuclear localization; a transcription factor and critical regulator of hematopoietic-cell development.

Result of the chromosomal anomaly

Hybrid gene
Description In the case described by Imagama et al. 2007, the translocation fuses RUNX1 exon 5 or exon 6 to MACROD1 exon 2, suggesting that the RUNX1 breakpoint lies in intron 6 and that alternative fusion splice variants are generated. The reciprocal MACROD1-RUNX1 fusion was also detected.
  

External links

Other databaset(11;21)(q13;q22) Mitelman database (CGAP - NCBI)
Other databaset(11;21)(q13;q22) CancerChromosomes (NCBI)

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

 
A t (11;21) (13;q22) in Ph-positive chronic myelogenous leukemia.
Wang TY, Raza A, Sait SN, Stein A, Schumer J, Sandberg AA.
Cancer Genet Cytogenet. 1988 Apr;31(2):187-91.
PMID 3162392
 
Two novel translocations disrupt the RUNX1 gene in acute myeloid leukemia.
Dai H, Xue Y, Pan J, Wu Y, Wang Y, Shen J, Zhang J.
Cancer Genet Cytogenet. 2007 Sep;177(2):120-4.
PMID 17854666
 
Estrogenically regulated LRP16 interacts with estrogen receptor alpha and enhances the receptor's transcriptional activity.
Han WD, Zhao YL, Meng YG, Zang L, Wu ZQ, Li Q, Si YL, Huang K, Ba JM, Morinaga H, Nomura M, Mu YM.
Endocr Relat Cancer. 2007 Sep;14(3):741-53.
PMID 17914104
 
LRP16 is fused to RUNX1 in monocytic leukemia cell line with t(11;21)(q13;q22).
Imagama S, Abe A, Suzuki M, Hayakawa F, Katsumi A, Emi N, Kiyoi H, Naoe T.
Eur J Haematol. 2007 Jul;79(1):25-31. Epub 2007 May 28.
PMID 17532767
 
GC-rich promoter elements maximally confers estrogen-induced transactivation of LRP16 gene through ERalpha/Sp1 interaction in MCF-7 cells.
Han WD, Si YL, Zhao YL, Li Q, Wu ZQ, Hao HJ, Song HJ.
J Steroid Biochem Mol Biol. 2008 Mar;109(1-2):47-56. Epub 2007 Dec 8.
PMID 18206366
 
LRP16 gene function based on bioinformatic analysis.
Yang B, Lu XC, Chi XH, Han WD, Yu L, Lou FD.
Chin J Cancer. 2009 Dec 5;28(12):1283-90.
PMID 19958623
 

Contributor(s)

Written12-2009Jean-Loup Huret, Yongquan Xue
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France (JLH); Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, PR China (YX)

Citation

This paper should be referenced as such :
Huret JL, Xue Y, . t(11;21)(q13;q22). Atlas Genet Cytogenet Oncol Haematol. December 2009 .
URL : http://AtlasGeneticsOncology.org/Anomalies/t1121q13q22ID1505.html

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indexed on : Sat Feb 6 15:46:21 CET 2010

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