Written | 2014-03 | Etienne 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 |
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. |
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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 (zinc finger MYND-type containing 11) |
Location | 10p15.3 |
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 (mbt domain containing 1) |
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 database | t(10;17)(p15;q21) |
arrayMap (UZH-SIB Zurich) | Topo ( C42) Morph ( 9861/3) - [auto + random 100 samples .. if exist ] [tabulated segments] |
REVIEW articles | automatic search in PubMed |
Last year articles | automatic search in PubMed |
All articles | automatic search in PubMed |
© Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Dec 14 18:26:23 CET 2020 |
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