Transcriptional activation of human LIM-HOX gene, hLH-2, in chronic myelogenous leukemia is due to a cis-acting effect of Bcr-Abl

Biochemical and Biophysical Research Communications
H K Wu, M D Minden

Abstract

DNA methylation plays an important role in gene regulation. A human LIM-HOX gene, namely hLH-2, was highly expressed in chronic myelogenous leukemia (CML) and located on chromosome 9q33-34.1, in the same region as the reciprocal translocation that creates the Bcr-Abl chimera of Philadelphia chromosome (H.-K. Wu et al., 1996, Oncogene 12, 1205-1212). To elucidate the mechanism of hLH-2 transcriptional activation, we studied the methylation status of hLH-2 in normal bone marrow and CML cells. When blots containing genomic DNA digested with Hpa II or Msp I were hybridized with full-length cDNA probe, it was discovered that hLH-2 was methylated in normal bone marrow cells in which hLH-2 was not expressed; in contrast, both alleles of the hLH-2 locus in CML cells were heavily hypomethylated. Furthermore, using a sensitive RT-PCR technique, we examined the expression of LH-2 in mouse x human hybrids and a wide array of mouse cell lines containing Abl or Bcr-Abl, and we failed to identify a consistent expression pattern in the cell lines tested. These results suggest that the transcriptional activation of hLH-2 in CML is likely due to a cis-acting effect, but not a trans-acting effect, of the Bcr-Abl fusion protein. Because hypomethyl...Continue Reading

References

Jul 10, 1992·Cell·A Bird
Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·A PerkinsS Cory
Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M A KelliherN Rosenberg
Jul 1, 1983·Analytical Biochemistry·A P Feinberg, B Vogelstein
Apr 21, 1995·Cell·P W LairdR Jaenisch
Jan 1, 1993·Mutation Research·R Holliday, G W Grigg
Jan 1, 1994·Human Molecular Genetics·P W Laird, R Jaenisch
Aug 4, 1993·Journal of the National Cancer Institute·J P IssaS B Baylin

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Citations

Oct 29, 2010·Clinical & Developmental Immunology·Heath A Smith, Douglas G McNeel
Aug 19, 2015·Cancer Metastasis Reviews·Stefan K ZöllnerJeffrey A Toretsky
Sep 28, 2002·Stem Cells·Bronwyn M Owens, Robert G Hawley

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