Expression of HOX genes in acute leukemia cell lines with and without MLL translocations.
In primary cells from acute leukemia patients, expression of the genes MEIS1, HOXA5, HOXA7 and HOXA9 has been reported to be correlated with the occurrence of MLL translocations. It was our aim to find out whether MLL mutant (MLLmu) and MLL wild-type (MLLwt) acute leukemia-derived cell lines might likewise be discriminated on the basis of HOX gene expression. Southern blot analysis, performed to verify the MLL status of the cells, showed that NOMO-1 was the only cell line not tested previously carrying a rearranged MLL gene. Fluorescence in situ hybridization analysis demonstrated that this cell line exhibited a reciprocal t(9;11)(q23;p22). Sequencing of RT-PCR products thereof identified unique MLL exon 10/AF-9 exon 5 fusion transcripts. We divided the acute leukemia-derived cell lines (n = 37) according to the results of Southern blot analysis into MLLmu (n = 19) and MLLwt (n = 18). Expression of HOX genes was then analyzed by applying reverse transcriptase-polymerase chain reaction, Northern and Western blot analyses. Acute myeloid leukemia (AML) cell lines expressed the HOX genes significantly more often than acute lymphoblastic (ALL) cell lines. In ALL, cells with MLL translocations expressed the genes 4 times more often than MLLwt cells. Most distinct was the correlation between MLL status and MEIS1 expression in ALL-derived cell lines: 8/8 MLLmu but 0/10 MLLwt cell lines expressed MEIS1. Northern and Western blot analysis confirmed that also HOXA9 and FLT3 were significantly more often and stronger expressed in MLLmu than in MLLwt ALL cell lines. These results suggest that MLL aberrations may regulate MEIS1 and HOXA9 gene expression in ALL-derived cell lines, while AML-derived cell lines express these genes independently of the MLL status.
Quentmeier
Hilmar
H
DSMZ--German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany. hqu@dsmz.de
Dirks
Wilhelm G
WG
Macleod
Roderick A F
RA
Reinhardt
Julia
J
Zaborski
Margarete
M
Drexler
Hans G
HG
D000208:Acute Disease; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D011495:Histone-Lysine N-Methyltransferase; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011519:Proto-Oncogenes; D014157:Transcription Factors; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C497422:KMT2A protein, human; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors; C097899:homeobox protein HOXA9; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase