NUP98-MLL fusion in human acute myeloblastic leukemia.
Posttranscriptional modifications of histones play important roles in the control of chromatin structure and transcription. H3K4 (histone H3 lysine 4) methylation by the SET domain of the trithorax-group protein MLL (mixed-lineage leukemia) is important for the control of homeobox (HOX) gene expression during development. MLL is tethered to the HOXA locus through interaction of its amino-terminus with menin. MLL fusion proteins associated with human leukemia contain the menin interaction peptide and frequently recruit H3K79 (histone H3 lysine 79) methylation activity. This allows sustained expression of HOXA genes important for cellular transformation. We have characterized a novel recurrent chromosomal aberration, inv(11)(p15q23), as an isolated chromosomal abnormality in 2 patients with acute myeloid leukemia. This aberration is predicted to result in the expression of an NUP98 (nucleoporin 98 kDa)-MLL fusion protein that is unable to interact with menin. As expected, low levels of HOXA gene expression were observed in the patients' samples. This fusion protein is predicted to participate in cellular transformation by activating MLL targets other than HOXA genes.
Kaltenbach
Sophie
S
INSERM U985, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif, France.
Soler
Gwendoline
G
Barin
Carole
C
Gervais
Carine
C
Bernard
Olivier A
OA
Penard-Lacronique
Virginie
V
Romana
Serge P
SP
D000328:Adult; D000368:Aged; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D007446:Chromosome Inversion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005801:Genes, Homeobox; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics* / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000235:genetics* / Q000378:metabolism; D050596:Oncogene Fusion; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism
D017931:DNA Primers; D004273:DNA, Neoplasm; D006657:Histones; D018398:Homeodomain Proteins; C497422:KMT2A protein, human; C105373:MEN1 protein, human; D028861:Nuclear Pore Complex Proteins; C465451:Nup98 protein, human; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; C088144:HoxA protein; D011495:Histone-Lysine N-Methyltransferase