Gene expression profiling of Polycomb, Hox and Meis genes in patients with acute myeloid leukaemia.
The Polycomb group (PcG) of genes is important for differentiation and cell-cycle regulation and is aberrantly expressed in several cancers. To analyse the role of deregulated PcG genes in acute myeloid leukaemia (AML), we determined by RQ-PCR the expression of the PcG genes BMI-1, MEL18, SCML2, YY1 and EZH2, and the downstream PcG targets HOXA4, HOXA9 and MEIS1 in diagnostic bone marrow samples from 126 AML patients. There was a general overexpression of the genes in AML patients compared to 20 healthy donors, except of HOXA4 and MEL18, which both displayed a wide range of expression levels within the AML subgroups. Among the AML patients with normal karyotype, a low HOXA4 level was associated with a shorter overall survival (P = 0.005). In addition, expression levels of MEL18 and EZH2 were significantly (P < 0.025) higher in patients with complex karyotype and lower in CBF-mutated patients. The t(8;21) vs. inv(16) positive patients showed significantly different expression of SCML2, BMI-1, YY1, HOXA9 and MEIS1 (P < or = 0.01). Comparisons between the PcG and PcG-regulated genes and a number of clinical and molecular data revealed correlations to genes involved in DNA methylation (DNMT1, DNMT3B), apoptosis (BAX, CASPASE 3) and multidrug-resistance (MDR1, MRP ) (P < 0.01). In conclusion, our data suggest that the role of PcG and PcG-regulated genes in leukaemogenesis varies between, as well as within karyotypic subgroups.
Grubach
Lykke
L
Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
Juhl-Christensen
Caroline
C
Rethmeier
Anita
A
Olesen
Lene Hyldahl
LH
Aggerholm
Anni
A
Hokland
Peter
P
Ostergaard
Mette
M
D017209:Apoptosis / Q000235:genetics; D019175:DNA Methylation; D018432:Drug Resistance, Multiple / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D063146:Polycomb-Group Proteins; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors
D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C097899:homeobox protein HOXA9; C073547:HOXA4 protein, human