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

2014-09-01   Mariana Emerenciano , Maria S Pombo-de-Oliveira , Rolf Marschalek , Claus Meyer 

1.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)

Clinics and Pathology


Infant acute myeloid leukemia (AML)

Phenotype stem cell origin


Poorly defined, only one case described to date, a 11 month-old boy (Coser et al., 2010).


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).


Atlas Image
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).


MLL dual color break apart rearrangement probe.

Genes Involved and Proteins

Gene name
KMT2A (myeloid/lymphoid or mixed lineage leukemia)
Dna rna description
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 description
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 (nebulette)
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 description
The Nebulette non-muscle isoform consists of 7 exons, encoding a 270 amino-acid protein with a molecular weight of 31,2 kDa.
Protein description
270 aa, 31,2 kDa.

Result of the Chromosomal Anomaly


Fusion gene MLL-NEBL and NEBL-MLL was detected by LDI-PCR (Coser et al., 2010).
Atlas Image
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).


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 protocole

Detection method RT-PCR.
Atlas Image
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).


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.


Pubmed IDLast YearTitleAuthors
203622302010Nebulette is the second member of the nebulin family fused to the MLL gene in infant leukemia.Cóser VM et al
233401732013Functional analysis of the two reciprocal fusion genes MLL-NEBL and NEBL-MLL reveal their oncogenic potential.Emerenciano M et al
250160622014Functional characterisation of different MLL fusion proteins by using inducible Sleeping Beauty vectors.Wächter K et al


Fusion gene

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


Mariana Emerenciano ; Maria S Pombo-de-Oliveira ; Rolf Marschalek ; Claus Meyer

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

Atlas Genet Cytogenet Oncol Haematol. 2014-09-01

Online version: http://atlasgeneticsoncology.org/haematological/1702/t(10;11)(p12;q23)

External Links