The human LASP1 gene is fused to MLL in an acute myeloid leukemia with t(11;17)(q23;q21).
The MLL gene at chromosome 11q23 is frequently rearranged in acute leukemia. Here we report the identification of a new MLL fusion partner in the case of an infant with AML-M4 and a t(11;17)(q23;q21) translocation. Fluorescence in situ hybridization (FISH) and RT-PCR analyses indicated a rearrangement of the MLL gene, but no fusion with previously identified MLL fusion partners at 17q, such as AF17 or MSF. Rapid amplification of cDNA ends (RACE) revealed an in-frame fusion of MLL to LASP1, a gene that is amplified and overexpressed in breast cancer. Retroviral transduction of myeloid progenitors demonstrated that MLL/LASP1 is the fourth known fusion of MLL with a cytoplasmic protein that has no in vitro transformation capability, thus establishing a potential subgroup among the MLL fusion proteins.
Strehl
Sabine
S
CCRI, Children's Cancer Research Institute, St. Anna Kinderspital, Vienna, Austria.
Borkhardt
Arndt
A
Slany
Robert
R
Fuchs
Uta E
UE
König
Margit
M
Haas
Oskar A
OA
D000208:Acute Disease; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D060588:LIM Domain Proteins; D007951:Leukemia, Myeloid / Q000235:genetics*; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins; D011519:Proto-Oncogenes; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014178:Translocation, Genetic
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C497422:KMT2A protein, human; C096353:LASP1 protein, human; D060588:LIM Domain Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase