inv(11)(q13q23) KMT2A/BTBD18

2012-03-01   Claus Meyer , Marta Susana Gallego , Jorge Rossi , Patricia Rubio , Adriana Medina , Rolf Marschalek , Maria Felice , Cristina Alonso , Adrian Mansini 

1.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)

Clinics and Pathology


Infant acute lymphoblastic leukemia (ALL)


Poorly defined, only one case described to date, a 9-months-old boy with Pro-B ALL (FAB L1) (Alonso et al., 2010).


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.


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).


Atlas Image
Partial G-banded karyogram for the inv(11)(q13q23), showing both chromosomes 11.

Cytogenetics morphological

46,XY,inv(11)(q13q23) as sole abnormality.

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).
Atlas Image
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.


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 at least 37 exons, encoding a 3969 amino-acid nuclear protein with a molecular weight of nearly 431 kDa.
Atlas Image
Schematic diagram of the exon/intron structure of the MLL gene (Nilson et al., 1996).
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
BTBD18 (BTB domain containing 18)
Protein description
712 amino acids; 78 kDa.

Result of the Chromosomal Anomaly

Atlas Image
Fusion sequence of the MLL-BTBD18 fusion transcript.


In frame fusion between the truncated MLL exon 10 and the truncated BTBD18 exon 3.



Detection protocole

RT-PCR (van Dongen et al., 1999; Alonso et al., 2010).
Atlas Image
Schematic diagram of the structure of the predicted MLL-BTBD18 fusion protein.


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).


Pubmed IDLast YearTitleAuthors
205983702010BTBD18: A novel MLL partner gene in an infant with acute lymphoblastic leukemia and inv(11)(q13;q23).Alonso CN et al
156267572005Diagnostic tool for the identification of MLL rearrangements including unknown partner genes.Meyer C et al
87038351996Exon/intron structure of the human ALL-1 (MLL) gene involved in translocations to chromosomal region 11q23 and acute leukaemias.Nilson I et al
176583952007A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial.Pieters R et al
162073532005Sequence and structural analysis of BTB domain proteins.Stogios PJ et al
106024111999Standardized 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 et al


Fusion gene

KMT2A/BTBD18 KMT2A (11q23.3) BTBD18 (11q12.1) COF 2054 2055


Claus Meyer ; Marta Susana Gallego ; Jorge Rossi ; Patricia Rubio ; Adriana Medina ; Rolf Marschalek ; Maria Felice ; Cristina Alonso ; Adrian Mansini

inv(11)(q13q23) KMT2A/BTBD18

Atlas Genet Cytogenet Oncol Haematol. 2012-03-01

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