RGD Reference Report - Methylation of the major breakpoint cluster region (M-bcr) in Philadelphia-positive CML. - Rat Genome Database

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Methylation of the major breakpoint cluster region (M-bcr) in Philadelphia-positive CML.

Authors: Mills, KI  Sproul, AM  Burnett, AK 
Citation: Mills KI, etal., Leukemia. 1993 May;7(5):707-11.
RGD ID: 11038783
Pubmed: PMID:7683349   (View Abstract at PubMed)

It has previously been shown that a cluster of HpaII sites with the potential to be methylated exist around exon b3 of the M-bcr region involved in the formation of the Philadelphia chromosome in chronic myeloid leukemia (CML). The degree of hypermethylation of these sites can be directly correlated with the percentage of immature cells, whilst progressive hypomethylation occurs during the maturation of the granulocyte lineage. We have examined samples obtained from CML patients at diagnosis, during chronic phase, and blast crisis to examine the degree of methylation of this region in the non-rearranged BCR gene and the rearranged BCR-ABL gene. A low degree of methylation of the non-rearranged gene, similar to that observed in normal individuals, was observed in diagnosis and chronic phase samples. Increased methylation was observed during blast crisis indicative of the presence of immature cells in the samples. In contrast, a significantly lower degree of methylation was observed in the rearranged BCR-ABL gene at the onset of blast crisis. Division of the samples into those patients who had lost exon b3 during the formation of the BCR/ABL gene and those that had retained exon b3 produced differing patterns of methylation during disease progression. The former group, who also expressed a b2-a2 mRNA, showed an increase in methylation of the non-rearranged BCR gene prior to and during blast crisis, with a inverse decrease in the methylation of the BCR/ABL gene. Those patients who had retained exon b3, and expressed a b3-a2 mRNA, showed no change in the extent of methylation of the BCR/ABL gene but did exhibit an increase in methylation of the BCR gene during blast crisis. The consequence of the differing degree of methylation during disease progression could affect, to some extent, the specificity of protein binding or RNA expression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
chronic myeloid leukemia disease_progressionIAGP 11038783DNA:methylation: :RGD 
chronic myeloid leukemia disease_progressionISOBCR (Homo sapiens)11038783; 11038783DNA:methylation: :RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bcr  (BCR activator of RhoGEF and GTPase)

Genes (Mus musculus)
Bcr  (BCR activator of RhoGEF and GTPase)

Genes (Homo sapiens)
BCR  (BCR activator of RhoGEF and GTPase)


Additional Information