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Aberrant promoter methylation of the retinoic acid receptor alpha gene in acute promyelocytic leukemia
- Source :
- Leukemia. 19:2241-2246
- Publication Year :
- 2005
- Publisher :
- Springer Science and Business Media LLC, 2005.
-
Abstract
- The retinoic acid receptor alpha (RARA) gene is disrupted by PML/RARA fusion in acute promyelocytic leukemia (APL). The P2 promoter of RARA, controlling the RARalpha2 isoform, contains an RA-responsive element and may be targeted in APL. To test whether aberrant methylation of P2 was involved, 47 APL at diagnosis, 16 APL at first relapse, 50 acute myeloid leukemia (AML) and 22 acute lymphoblastic leukemia (ALL) were tested by methylation-specific polymerase chain reaction. RARA P2 methylation was highly associated with APL (APL: 25/63 vs AML/ALL: 2/75, P0.0001). P2 methylation occurred at similar frequencies in APL at diagnosis and relapse, suggesting it was an initiating leukemogenic event. In the APL line NB4, RARalpha2 was not expressed, with the untranslocated RARA shown to be P2 methylated. 5-Azacytadine treatment of NB4 led to progressive P2 demethylation and re-expression of RARalpha2, confirming that RARA methylation collaborated with PML/RARA in totally suppressing RARalpha. In APL, RARA P2 methylation was unrelated to gender, age, presenting leukocyte counts and additional cytogenetic aberrations. For APL patients receiving all-trans retinoic acid for induction, P2 methylation did not affect the complete remission rates and survivals. RARA is the first myeloid-specific transcription factor shown to be dysregulated by both translocation and aberrant methylation.
- Subjects :
- Acute promyelocytic leukemia
Cancer Research
medicine.medical_specialty
Receptors, Retinoic Acid
Retinoic acid
Tretinoin
Biology
Polymerase Chain Reaction
Fusion gene
chemistry.chemical_compound
Leukemia, Promyelocytic, Acute
Recurrence
immune system diseases
Internal medicine
medicine
Humans
Promoter Regions, Genetic
neoplasms
Hematology
Retinoic Acid Receptor alpha
Remission Induction
Myeloid leukemia
Biological Transport
Methylation
DNA Methylation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
medicine.disease
Gene Expression Regulation, Neoplastic
Survival Rate
Leukemia
Oncology
chemistry
Leukemia, Myeloid
Retinoic acid receptor alpha
Acute Disease
Cancer research
Subjects
Details
- ISSN :
- 14765551 and 08876924
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Leukemia
- Accession number :
- edsair.doi.dedup.....a78c5426c515a168dcb2bd9532c6bf02