ABL1 methylation in Ph-positive ALL is exclusively associated with the P210 form of BCR-ABL

P. J. Shteper, Z. Siegfried, F. A. Asimakopoulos, G. A. Palumbo, E. A. Rachmilewitz, Y. Ben-Neriah, D. Ben-Yehuda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

In human Ph-positive leukemia there is a clear association of different forms of the BCR-ABL oncogene with distinct types of leukemia. The P190 form of BCR-ABL is rarely observed in chronic myeloid leukemia (CML) but is present in 50% of Ph-positive acute lymphoblastic leukemia (ALL). In contrast, the P210 form is observed both in CML and 50% of Ph-positive ALL. Methylation of the proximal promoter of the ABL1 gene has been shown to be a nearly universal event associated with clinical progression of CML. This raises the question of whether methylation of the ABL1 promoter is an epigenetic modification also associated with Ph-positive ALL. To study this issue, we used methylation-specific PCR and bisulfite sequencing to determine the methylation status of the ABL1 promoter in 18 Ph-positive ALL samples. We report here that gene-specific ABL1 promoter methylation is associated mainly with the P210 form of BCR-ABL and not the P190 form. While six out of the seven P210-positive ALL samples had ABL1 promoter methylation, none of the 11 P190-positive ALL samples demonstrated ABL1 promoter methylation. In addition, we estimated the extent and relative abundance of ABL1 promoter methylation in several Ph-positive ALL samples and compared it to the methylation pattern in chronic, accelerated and blastic crisis phases of CML. We put forth a model that correlates the different types of leukemias with the different levels of ABL1 promoter methylation.

Original languageAmerican English
Pages (from-to)575-582
Number of pages8
JournalLeukemia
Volume15
Issue number4
DOIs
StatePublished - 2001

Bibliographical note

Funding Information:
This study was supported by grants from the Gabriella Rich Leukemia Fund, the Foulkes Foundation, the Office of the Chief Scientist of the State of Israel, the Israel Science Foundation, the Yael Foundation, and the Golda Meir Fellowship Fund. We thank Ilana Sverdlin for her skilled technical assistance.

Keywords

  • ABL
  • Acute lymphoblastic leukemia
  • Chronic myeloid leukemia
  • Methylation
  • Philadelphia chromosome

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