t(11;17)(q23;q12-21) KMT2A/LASP1

2005-08-01   Sabine Strehl 

1.Childrens Cancer Research Institute, Kinderspitalgasse 6, A-1090 Vienna, Austria

Clinics and Pathology

Disease

infant acute myeloid leukemia AML-M4

Epidemiology

only one case described so far

Prognosis

insufficient data; of note: the only patient described, remains in complete remission >8 years

Cytogenetics

Note

so far three MLL fusion partners, namely LASP1 (in the t(11;17) herein described), MLLT6 (alias AF17) (in another t(11;17)(q23;q12-21), and ACACA (also in another t(11;17)(q23;q12-21) have been identified in 17q12-21; these translocations cannot be distinguished cytogenetically and the accurate detection of the specific fusion gene requires RT-PCR or refined FISH analysis

Cytogenetics morphological

sole abnormality

Genes Involved and Proteins

Gene name
KMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location
11q23.3
Dna rna description
37 exons, spanning over 100 kb; transcription in a centromeric to telomeric direction; 13 and 15 kb mRNA; coding sequence: 11.9 kb
Protein description
431 kDa; contains two DNA binding motifs (an AT hook, and Zinc fingers), a DNA methyl transferase motif, and a bromodomain; transcriptional regulatory factor; nuclear localization
Gene name
LASP1 (LIM and SH3 protein)
Location
17q12
Note
previously LASP1 and MLLT6 (alis AF17) were mapped to 17q21, but according to the most recent genome assembly built and recent FISH data both genes are localized in 17q12 and proximal to RARA
Dna rna description
7 exons spanning about 50 kb of genomic DNA; 3845 bp mRNA, 783 bp coding sequence; ubiquitous expression
Protein description
LASP1 encodes a member of a LIM protein subfamily; contains a LIM motif, two actin-binding domains, and an SH3 domain; cytoplasmic localization

Result of the Chromosomal Anomaly

Transcript

5MLL - 3LASP1; also the reciprocal 5LASP1 - 3MLL is present
Atlas Image
Schematic representation of MLL, LASP1, and the putative MLL-LASP1 and LASP1-MLL fusion proteins.

Description

the C-terminal SH3 domain of LASP1 is fused to the N-terminal portion of MLL retaining the AT-hook DNA-binding domain and the DNA methyltransferase motif (MT)

Bibliography

Pubmed IDLast YearTitleAuthors
156761552005Acute myelocytic leukemia with t(11;17)(q23;q12-q21) involves a fusion of MLL and AF17.Moore SD et al
125279182003The human LASP1 gene is fused to MLL in an acute myeloid leukemia with t(11;17)(q23;q21).Strehl S et al

Summary

Fusion gene

KMT2A/LASP1 KMT2A (11q23.3) LASP1 (17q12) TIC
Atlas Image
t(11;17)(q23;q12-21) G- banding - Courtesy Melanie Zenger and Claudia Haferlach.

Citation

Sabine Strehl

t(11;17)(q23;q12-21) KMT2A/LASP1

Atlas Genet Cytogenet Oncol Haematol. 2005-08-01

Online version: http://atlasgeneticsoncology.org/haematological/1367/t(11;17)(q23;q12-21)

External Links