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t(10;17)(p15;q21) ZMYND11/MBTD1

Written2014-03Etienne De Braekeleer, Nathalie Douet-Guilbert, Audrey Basinko, Marie-Josée Le Bris, Frédéric Morel, Marc De Braekeleer
Cytogenetics Laboratory, Faculty of Medicine, University of Brest, France

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Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1234

Clinics and Pathology

Disease Acute myeloid leukemia (AML), poorly differentiated, AML without maturation or with minimal maturation (AML-M0, and AML-M1)
Epidemiology This is a rare chromosomal rearrangement, only reported in four cases of AML without or with minimal maturation, without molecular characterization (Pollak and Hagemeijer, 1987; Shah et al., 2001; Barjesteh van Waalwijk et al., 2003; Dicker et al., 2007). We add two cases with molecular cytogenetic studies (Tempescul et al., 2007; De Braekeleer et al., 2014).There were 2 cases of AML-M0 and 4 cases of AML-M1.
Clinics Patients were aged 11, 13, 16 and 40 years. There were 3 male and 3 female patients.
Treatment Treatments of the patients reported in Tempescul et al. 2007, De Braekeleer et al. 2014 were the following: (P1) induction therapy followed by three consolidation courses leading to complete remission; (P2) induction therapy followed by consolidation therapy leading to complete remission, then relapse and second complete remission, then bone marrow transplantation.
Evolution (P1) alive in complete remission 71 months following diagnosis; (P2) died 37 months following the initial diagnosis. Another patient reported in the literature was in complete remission at 42 months after diagnosis.

Cytogenetics

Note The t(10;17)(p15;q21) involves two genes that were not previously reported to form a putative fusion gene.
Cytogenetics Morphological t(10;17)(p15;q21) is identified by banding cytogenetics.
Cytogenetics Molecular To determine the position of the breakpoints on chromosomes 10 and 17, BACs located in the bands of interest were used as probes in FISH experiments. Analysis with RP11-387K19 showed that one signal hybridized to the normal chromosome 10, and the other split and hybridized to both der(10) and der(17). Analysis with RP11-326B24 showed that one signal hybridized to the normal chromosome 17, and the other split and hybridized to both der(17) and der(10). Co-hybridization with both BAC clones showed two fusion signals. RP11-387K19 contains the ZMYND11 gene and RP11-326B24 the MBTD1 gene.
 
  FISH with BACs RP11-387K19 (spectrum orange, located in 10p15 and containing ZMYND11) and RP11-326B24 (spectrum green, located in 17q21 and containing MBTD1) showing co-hybridization.

Genes involved and Proteins

Gene Name ZMYND11
Location 10p15.3 (according to UCSC Genome Browser on Human Feb. 2009 (GRCh37/hg19) Assembly)
Dna / Rna The ZMYND11 gene contains 15 exons, of which 14 are coding, spanning 120 kb. Different isoforms are generated by seven alternatively spliced transcript variants (Hateboer et al., 1995).
Protein The protein localizes to the nucleus and contains 3 motifs involved in transcription regulation: a PHD finger and bromodomain in its N-terminal half, and a MYND domain (conserved 2-zinc finger motif) at its C terminus. The MYND domain interacts with the N-CoR/mSin3/HDAC1 complex that causes transcriptional repression (Masselink and Bernards, 2000).
Gene Name MBTD1
Location 17q21.33
Dna / Rna The MBTD1 gene contains 17 exons, of which 15 are coding, spanning 82 kb. Seven transcript variants are known (Eryilmaz et al., 2009).
Protein MBTD1 localizes to the nucleus and contains a FCS-type zinc finger at the N-terminus with putative regulatory function and four MBT (malignant brain tumor) repeats at the C-terminus. MBTD1 is a putative Polycomb group protein, which are known to maintain the transcriptionally repressive state of genes, probably via chromatin remodeling (Nady 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

High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients.
Barjesteh van Waalwijk van Doorn-Khosrovani S, Erpelinck C, van Putten WL, Valk PJ, van der Poel-van de Luytgaarde S, Hack R, Slater R, Smit EM, Beverloo HB, Verhoef G, Verdonck LF, Ossenkoppele GJ, Sonneveld P, de Greef GE, Lowenberg B, Delwel R.
Blood. 2003 Feb 1;101(3):837-45. Epub 2002 Oct 3.
PMID 12393383
 
Recurrent translocation (10;17)(p15;q21) in acute poorly differentiated myeloid leukemia likely results in ZMYND11-MBTD1 fusion.
De Braekeleer E, Auffret R, Douet-Guilbert N, Basinko A, Le Bris MJ, Morel F, De Braekeleer M.
Leuk Lymphoma. 2014 May;55(5):1189-90. doi: 10.3109/10428194.2013.820292. Epub 2013 Aug 5.
PMID 23915195
 
Trisomy 13 is strongly associated with AML1/RUNX1 mutations and increased FLT3 expression in acute myeloid leukemia.
Dicker F, Haferlach C, Kern W, Haferlach T, Schnittger S.
Blood. 2007 Aug 15;110(4):1308-16. Epub 2007 May 7.
PMID 17485549
 
Structural studies of a four-MBT repeat protein MBTD1.
Eryilmaz J, Pan P, Amaya MF, Allali-Hassani A, Dong A, Adams-Cioaba MA, Mackenzie F, Vedadi M, Min J.
PLoS One. 2009 Oct 20;4(10):e7274. doi: 10.1371/journal.pone.0007274.
PMID 19841675
 
BS69, a novel adenovirus E1A-associated protein that inhibits E1A transactivation.
Hateboer G, Gennissen A, Ramos YF, Kerkhoven RM, Sonntag-Buck V, Stunnenberg HG, Bernards R.
EMBO J. 1995 Jul 3;14(13):3159-69.
PMID 7621829
 
The adenovirus E1A binding protein BS69 is a corepressor of transcription through recruitment of N-CoR.
Masselink H, Bernards R.
Oncogene. 2000 Mar 16;19(12):1538-46.
PMID 10734313
 
Histone recognition by human malignant brain tumor domains.
Nady N, Krichevsky L, Zhong N, Duan S, Tempel W, Amaya MF, Ravichandran M, Arrowsmith CH.
J Mol Biol. 2012 Nov 9;423(5):702-18. doi: 10.1016/j.jmb.2012.08.022. Epub 2012 Sep 4.
PMID 22954662
 
Abnormalities of the short arm of chromosome 9 with partial loss of material in hematological disorders.
Pollak C, Hagemeijer A.
Leukemia. 1987 Jul;1(7):541-8. (REVIEW)
PMID 3312844
 
Widespread bone disease in acute myeloid leukaemia.
Shah D, Bond M, Kilby AM, Patterson KG.
Leuk Lymphoma. 2001 Nov-Dec;42(6):1309-14.
PMID 11911413
 
Translocation (10;17)(p15;q21) is a recurrent anomaly in acute myeloblastic leukemia.
Tempescul A, Guillerm G, Douet-Guilbert N, Morel F, Le Bris MJ, De Braekeleer M.
Cancer Genet Cytogenet. 2007 Jan 1;172(1):74-6.
PMID 17175384
 

Citation

This paper should be referenced as such :
Braekeleer E De, N Douet-Guilbert, A Basinko, Bris MJ Le, F Morel, Braekeleer M De
t(10;17)(p15;q21) ZMYND11/MBTD1
Atlas Genet Cytogenet Oncol Haematol. 2014;18(10):754-756.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t1017p15q21ID1234.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(10;17)(p15;q21) ZMYND11/MBTD1

External links

Mitelman databaset(10;17)(p15;q21) [Case List]    t(10;17)(p15;q21) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
Disease databaset(10;17)(p15;q21) ZMYND11/MBTD1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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