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t(10;11)(p12;q23) KMT2A/NEBL

Written2014-09Claus Meyer, Mariana Emerenciano, Maria S Pombo-de-Oliveira, Rolf Marschalek
Institute of Pharmaceutical Biology/ZAFES/Diagnostic Center of Acute Leukemia (DCAL), Goethe-University of Frankfurt, Max-von-Laue Str. 9, Frankfurt/Main, Germany (CM, RM); Hematology-Oncology Pediatric Program, CPq Instiuto Nacional de Cancer, Rio de Janeiro, Brazil (ME, MSPO)

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ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1702

Clinics and Pathology

Disease Infant acute myeloid leukemia (AML)
Phenotype / cell stem origin AML-M5.
Epidemiology Poorly defined, only one case described to date, a 11 month-old boy (Coser et al., 2010).
Prognosis This infant was treated according to AML-BFM98 backbone adapted protocol and died 1 month later while in the aplastic phase of treatment (Coser et al., 2010).


  The probe was hybridized to interphase nuclei and displayed one split hybridization (arrow) signal that indicates translocation with an unknown partner gene (Coser et al., 2010).
Probes MLL dual color break apart rearrangement probe.

Genes involved and Proteins

Gene Name KMT2A
Location 11q23
Dna / Rna The Mixed-Lineage Leukemia gene consists of 37 exons, encoding a 3969 amino-acid nuclear protein with a molecular weight of nearly 431 kDa.
Protein 431 kDa; contains two DNA binding motifs (a AT hook and Zinc fingers), and a DNA methyl transferase motif; wide expression; nuclear localisation; transcriptional regulatory factor.
Gene Name NEBL
Location 10p12
Note Nebulette, non-muscle isoform.
There exists also a sacomeric isoform of the NEBL gene. Nebulette is the second member of the nebulin family fused to MLL.
Dna / Rna The Nebulette non-muscle isoform consists of 7 exons, encoding a 270 amino-acid protein with a molecular weight of 31,2 kDa.
Protein 270 aa, 31,2 kDa.

Result of the chromosomal anomaly

Hybrid gene
Note Fusion gene MLL-NEBL and NEBL-MLL was detected by LDI-PCR (Coser et al., 2010).
  A. Left: Long-distance inverse polymerase chain reaction (LDI-PCR) analysis of both derivatives using genomic DNA. Lane M, size marker; lane 1, LDI-PCR analysis of der(11) showing the wild-type (wt) band and the der(11) band (asterisk); lane 2, LDI-PCR analysis of der(10) showing the wt band and the der(10) band (asterisk). Right: Genomic breakpoint sequence alignment of both derivatives (MLL/NEBL and NEBL/MLL) with respective wt sequences (Coser et al., 2010). B. The genetic fusion of MLL and NEBL in this AML patient occurred within the non-muscle form of the NEBL gene (intron 3) and within the known breakpoint cluster region of MLL (intron 9). The gene structures are indicated and the recombination site is indicated by a dashed line (Emerenciano et al., 2013). C. RT-PCR analyses of MLL-NEBL and NEBL-MLL fusion transcripts (Emerenciano et al., 2013).
Description In the described patient MLL exons 1-9 are fused to NEBL (non-muscle isoform) exons 4-6 due to translocation between MLL intron 9 and NEBL (non-muscle isoform) intron 3. NEBL (non-muscle isoform) exons 1-3 are fused to MLL exons 10-37 due to translocation between NEBL (non-muscle isoform) intron 3 and MLL intron 10.
Detection Detection method RT-PCR.
Fusion Protein
  Size and location of functional domains of the MLL wt, NEBL wt, and of the MLL-NEBL fusion protein. AT, AT hook, SNL, subnuclear localization; MT, methyltransferase; BD, binding domain; TAD, transcriptional activation domain; PHD, plant homeo domain; SET, Su(var)3e9; Enhancer-of-zeste, Trithorax; NEBU, nebulette units; SH3, SRC homology 3. (Coser et al., 2010).
Description The 1582 amino acid big fusion protein retains a major portion of MLL, including those domains known to be essential for leukemic transformation: the AT-hooks and the DNA methyltransferase domain (DNMT) which is fused two nebulin modules, the truncated serine-rich linker region and the SH3 domain of the NEBL protein.

To be noted

Two other studies suggest that the reciprocal fusion gene NEBL-MLL might be of biological importance (Emerenciano et al., 2013; Wächter et al., 2014).

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.


Nebulette is the second member of the nebulin family fused to the MLL gene in infant leukemia.
Coser VM, Meyer C, Basegio R, Menezes J, Marschalek R, Pombo-de-Oliveira MS.
Cancer Genet Cytogenet. 2010 Apr 15;198(2):151-4. doi: 10.1016/j.cancergencyto.2009.12.013.
PMID 20362230
Functional analysis of the two reciprocal fusion genes MLL-NEBL and NEBL-MLL reveal their oncogenic potential.
Emerenciano M, Kowarz E, Karl K, de Almeida Lopes B, Scholz B, Bracharz S, Meyer C, Pombo-de-Oliveira MS, Marschalek R.
Cancer Lett. 2013 May 10;332(1):30-4. doi: 10.1016/j.canlet.2012.12.023. Epub 2013 Jan 20.
PMID 23340173
Functional characterisation of different MLL fusion proteins by using inducible Sleeping Beauty vectors.
Wachter K, Kowarz E, Marschalek R.
Cancer Lett. 2014 Oct 1;352(2):196-202. doi: 10.1016/j.canlet.2014.06.016. Epub 2014 Jul 9.
PMID 25016062


This paper should be referenced as such :
C Meyer, M Emerenciano, MS Pombo-de-Oliveira, R Marschalek
t(10;11)(p12;q23) KMT2A/NEBL
Atlas Genet Cytogenet Oncol Haematol. 2015;19(4):308-310.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(10;11)(p12;q23) KMT2A/NEBL

External links

KMT2A (11q23.3) NEBL (10p12.31)

Mitelman databaset(10;11)(p12;q23) [Case List]    t(10;11)(p12;q23) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
TICdbKMT2A/NEBL  KMT2A (11q23.3) NEBL (10p12.31)
Disease databaset(10;11)(p12;q23) KMT2A/NEBL
REVIEW articlesautomatic search in PubMed
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