Activation of HLXB9 by juxtaposition with MYB via formation of t(6;7)(q23;q36) in an AML-M4 cell line (GDM-1).
Mutation or dysregulation of related homeobox genes occurs in leukemia. Using RT-PCR, we screened members of the EHG family of homeobox genes, comprising EN1 (at 2q14), GBX2 (at 2q36), and EN2, GBX1, and HLXB9 (at 7q36), for dysregulation in acute myeloid leukemia (AML) cell lines indicated by chromosomal breakpoints at these sites. Only one EHG-family gene was expressed, HLXB9, in cell line GDM-1 (AML-M4). Karyotypic analysis of GDM-1 revealed a unique t(6;7)(q23;q35), also present in the patient. Fluorescence in situ hybridization analysis showed chromosomal breakpoints close to the region upstream of HLXB9, at 7q36, a region rearranged in certain AML patients, and at 6q23 upstream of MYB, a gene activated in leukemia. Detailed expression analysis suggested ectopic activation of HLXB9 occurred via juxtaposition with regions upstream of MYB, which was highly expressed in GDM-1. Our data identified a cell line model for a novel leukemic translocation involving MYB with HLXB9, further implicating HLXB9 in leukemogenesis.
Nagel
Stefan
S
DSMZ-German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany.
Kaufmann
Maren
M
Scherr
Michaela
M
Drexler
Hans G
HG
MacLeod
Roderick A F
RA
D045744:Cell Line, Tumor; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D020732:Cytogenetic Analysis / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020570:Genes, myb / Q000502:physiology*; D018922:HL-60 Cells / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells / Q000737:chemistry / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells / Q000737:chemistry / Q000378:metabolism; D020014:K562 Cells / Q000737:chemistry / Q000378:metabolism; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics* / Q000473:pathology; D020598:Proto-Oncogene Proteins c-myb / Q000096:biosynthesis; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014178:Translocation, Genetic / Q000235:genetics*; D020298:U937 Cells / Q000737:chemistry / Q000378:metabolism
D018398:Homeodomain Proteins; C490003:MNX1 protein, human; D020598:Proto-Oncogene Proteins c-myb; D014157:Transcription Factors