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

• Published in: Leukemia Vol. 15; no. 4; pp. 575 - 582
• Main Authors: SHTEPER, P. J, SIEGFRIED, Z, ASIMAKOPOULOS, F. A, PALUMBO, G. A, RACHMILEWITZ, E. A, BEN-NERIAH, Y, BEN-YEHUDA, D
• Format: Conference Proceeding Journal Article
• Language: English
• Published: London Nature Publishing 01.04.2001; Nature Publishing Group
• Subjects: Abl protein; Abl1 gene; Acute lymphoblastic leukemia; Adolescent; Adult; Aged; Ataxia Telangiectasia Mutated Proteins; BCR gene; BCR protein; Biological and medical sciences; Bisulfite; Cell Cycle Proteins; Chromosomes; Chronic myeloid leukemia; DNA Methylation; DNA-Binding Proteins; Epigenetics; Fusion protein; Genes, abl; Hematologic and hematopoietic diseases; Hematology; Humans; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphatic leukemia; Medical sciences; Methylation; Middle Aged; Myeloid leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Promoter Regions, Genetic; Protein-Serine-Threonine Kinases - genetics; Proteins; Relative abundance; Tumor Suppressor Proteins; Jerusalem Israel; Israel; Chromosomal aberration; Human; Transcription promoter; Acute; Malignant hemopathy; Philadelphia chromosome; Repair gene; Myeloproliferative syndrome; Chronic; Lymphoproliferative syndrome; C-Onc gene; Chronic myelocytic leukemia; Cytogenetics; Abnormal chromosome; Genetics; Acute lymphocytic leukemia; Methylation; Comparative study; Hybrid gene; Protooncogene; Tumor suppressor gene; Chromosome translocation
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2402026

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.