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ABL1 promoter methylation can exist independently of BCR-ABL transcription in chronic myeloid leukemia hematopoietic progenitors.

Publication ,  Journal Article
Sun, B; Jiang, G; Zaydan, MA; La Russa, VF; Safah, H; Ehrlich, M
Published in: Cancer Res
September 15, 2001

Formation of the hybrid BCR-ABL gene is responsible for >95% of chronic myeloid leukemia (CML). The alternative, downstream ABL promoter (Pa), which is usually retained in this chimeric oncogene, was reported to be methylated in many CML patients, but there has been controversy as to whether this methylation is a frequent change in bone marrow (BM) in early chronic phase (CP) or only past this stage. Also, the relevance of Pa promoter methylation to BCR-ABL expression in CML is unclear. We examined methylation of the ABL Pa promoter in uncultured BM samples and in colonies derived from their hematopoietic precursor cells by bisulfite and PCR-based assays (combined bisulfite restriction analysis and methylation-specific PCR). BM from seven CP CML patients at diagnosis had about 20-60% of the copies of the ABL Pa promoter methylated. No Pa methylation was detected in normal BMs or colonies derived from them. In contrast, most colonies from CP CML patients had Pa methylation. Surprisingly, 18-49% of the CML-derived colonies with this methylation reproducibly had no detectable BCR-ABL RNA on nested reverse transcription-PCR. Furthermore, the percentage of BCR-ABL RNA-positive colonies was almost same among the colonies not displaying Pa methylation as among the colonies in which this methylation was found. We conclude that ABL Pa methylation is often an early marker of CML in hematopoietic precursors and in total mononuclear BM cells but that it is not associated with an increased frequency of BCR-ABL RNA-positive cells. This methylation might be emblematic of cancer-associated hypermethylation elsewhere in the genome with the consequent silencing of tumor suppressor genes seen in many malignancies.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

September 15, 2001

Volume

61

Issue

18

Start / End Page

6931 / 6937

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Molecular Sequence Data
  • Middle Aged
  • Male
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sun, B., Jiang, G., Zaydan, M. A., La Russa, V. F., Safah, H., & Ehrlich, M. (2001). ABL1 promoter methylation can exist independently of BCR-ABL transcription in chronic myeloid leukemia hematopoietic progenitors. Cancer Res, 61(18), 6931–6937.
Sun, B., G. Jiang, M. A. Zaydan, V. F. La Russa, H. Safah, and M. Ehrlich. “ABL1 promoter methylation can exist independently of BCR-ABL transcription in chronic myeloid leukemia hematopoietic progenitors.Cancer Res 61, no. 18 (September 15, 2001): 6931–37.
Sun B, Jiang G, Zaydan MA, La Russa VF, Safah H, Ehrlich M. ABL1 promoter methylation can exist independently of BCR-ABL transcription in chronic myeloid leukemia hematopoietic progenitors. Cancer Res. 2001 Sep 15;61(18):6931–7.
Sun B, Jiang G, Zaydan MA, La Russa VF, Safah H, Ehrlich M. ABL1 promoter methylation can exist independently of BCR-ABL transcription in chronic myeloid leukemia hematopoietic progenitors. Cancer Res. 2001 Sep 15;61(18):6931–6937.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

September 15, 2001

Volume

61

Issue

18

Start / End Page

6931 / 6937

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Molecular Sequence Data
  • Middle Aged
  • Male
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Humans