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inv(11)(q13q23) KMT2A::BTBD18

Written2012-03Adrian Mansini, Claus Meyer, Marta Susana Gallego, Jorge Rossi, Patricia Rubio, Adriana Medina, Rolf Marschalek, Maria Felice, Cristina Alonso
Dept. Hematology, Oncology, Hosp. Pediatria Garrahan, Buenos Aires, Argentina (AMa, PR, AMe, MF, CA); Agencia Nacional de Promocion Cientifica y Tecnologica, MINCyT, Argentina (AMa); Dept. Genetics, Hosp. Pediatria Garrahan, Buenos Aires, Argentina (MSG); Dept. Immunology, Hosp. Pediatria Garrahan, Buenos Aires, Argentina (JR); Inst. Pharm Biology, Goethe-University, Biocenter/DCAL, Max-von-Laue-Str. 9, D-60438 Frankfurt/Main, Germany (CM, RM)

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ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id 1585

Clinics and Pathology

Disease Infant acute lymphoblastic leukemia (ALL)
Epidemiology Poorly defined, only one case described to date, a 9-months-old boy with Pro-B ALL (FAB L1) (Alonso et al., 2010).
Evolution Patient achieved complete remission on day 33 of treatment and 5 months since diagnosis presented a bone marrow relapse. The patient had no available compatible donor and he did not receive a second line treatment and palliative care was administered. He died due to progressive disease.
Prognosis Infant-ALL with 11q23 abnormality/MLL gene rearrangement has been defined as a type of leukemia with poor prognosis (Pieters et al., 2007). The patient relapsed at +5 months and died due to progressive disease.


Fusion gene MLL-BTBD18 (Alonso et al., 2010) was detected by LDI-PCR, as described (Meyer et al., 2005).


Cytogenetics Morphological 46,XY,inv(11)(q13q23) as sole abnormality.
  Partial G-banded karyogram for the inv(11)(q13q23), showing both chromosomes 11.
Cytogenetics Molecular Split-FISH analysis revealed two signals corresponding to the 3' and the 5' probes, both on the long arm of chromosome 11 (Alonso et al., 2010).
  Split-FISH: The hybridization pattern for the chromosome with the MLL-BTBD18 rearrangement is one red/one green signal, while the yellow signal represents the germline MLL allele.
Probes MLL Dual Color Break Apart Rearrangement Probe.

Genes involved and Proteins

Gene NameKMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location 11q23.3
  Schematic diagram of the exon/intron structure of the MLL gene (Nilson et al., 1996).
Dna / Rna The Mixed-Lineage Leukemia gene consists of at least 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 NameBTBD18 (BTB domain containing 18)
Location 11q12.1
Protein 712 amino acids; 78 kDa.

Result of the chromosomal anomaly

Hybrid gene
  Fusion sequence of the MLL-BTBD18 fusion transcript.
Description In frame fusion between the truncated MLL exon 10 and the truncated BTBD18 exon 3.
Transcript MLL-BTBD18.
Detection RT-PCR (van Dongen et al., 1999; Alonso et al., 2010).
Fusion Protein
  Schematic diagram of the structure of the predicted MLL-BTBD18 fusion protein.
Description Fusion protein of 1989 amino acids containing 1374 codons from the amino-terminal region of MLL and 614 codons from the carboxy terminal portion of the BTBD18 protein, plus "fusion codon" consisting of two nucleotides derived from the MLL gene sequence and one from BTBD18 gene sequence. The chimeric protein of 1989 amino acids 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). The C-terminal sequences are derived from the BTBD18 protein, a new fusion partner. The fusion occurred with in the BTB/POZdomain of BTBD18 (Alonso et al., 2010).

To be noted

Additional cases are needed to delineate the epidemiology and prognosis of this entity, even when MLL abnormalities are associated with poor prognosis, especially when they are identified in infant leukemias (Pieters et al., 2007).


BTBD18: A novel MLL partner gene in an infant with acute lymphoblastic leukemia and inv(11)(q13;q23).
Alonso CN, Meyer C, Gallego MS, Rossi JG, Mansini AP, Rubio PL, Medina A, Marschalek R, Felice MS.
Leuk Res. 2010 Nov;34(11):e294-6. Epub 2010 Jul 2.
PMID 20598370
Diagnostic tool for the identification of MLL rearrangements including unknown partner genes.
Meyer C, Schneider B, Reichel M, Angermueller S, Strehl S, Schnittger S, Schoch C, Jansen MW, van Dongen JJ, Pieters R, Haas OA, Dingermann T, Klingebiel T, Marschalek R.
Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):449-54. Epub 2004 Dec 30.
PMID 15626757
Exon/intron structure of the human ALL-1 (MLL) gene involved in translocations to chromosomal region 11q23 and acute leukaemias.
Nilson I, Lochner K, Siegler G, Greil J, Beck JD, Fey GH, Marschalek R.
Br J Haematol. 1996 Jun;93(4):966-72.
PMID 8703835
A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial.
Pieters R, Schrappe M, De Lorenzo P, Hann I, De Rossi G, Felice M, Hovi L, LeBlanc T, Szczepanski T, Ferster A, Janka G, Rubnitz J, Silverman L, Stary J, Campbell M, Li CK, Mann G, Suppiah R, Biondi A, Vora A, Valsecchi MG.
Lancet. 2007 Jul 21;370(9583):240-50.
PMID 17658395
Sequence and structural analysis of BTB domain proteins.
Stogios PJ, Downs GS, Jauhal JJ, Nandra SK, Prive GG.
Genome Biol. 2005;6(10):R82. Epub 2005 Sep 15.
PMID 16207353
Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia.
van Dongen JJ, Macintyre EA, Gabert JA, Delabesse E, Rossi V, Saglio G, Gottardi E, Rambaldi A, Dotti G, Griesinger F, Parreira A, Gameiro P, Diaz MG, Malec M, Langerak AW, San Miguel JF, Biondi A.
Leukemia. 1999 Dec;13(12):1901-28. (REVIEW)
PMID 10602411


This paper should be referenced as such :
Mansini, A ; Meyer, C ; Gallego, MS ; Rossi, J ; Rubio, P ; Medina, A ; Marschalek, R ; Felice, M ; Alonso, C
Atlas Genet Cytogenet Oncol Haematol. 2012;16(7):502-505.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 inv(11)(q13q23) KMT2A/BTBD18

External links

KMT2A (11q23.3) BTBD18 (11q12.1)

Mitelman databaseinv(11)(q13q23)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
COSMIC_fusionKMT2A/BTBD18 KMT2A (11q23.3) BTBD18 (11q12.1)   [fusion2054]   [fusion2055]  
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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indexed on : Fri Oct 8 16:35:39 CEST 2021

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