Sangeetha Sampath1, Pratibha Misra2, Sandeep Kumar Yadav3, Sanjeevan Sharma4, Venkatesan Somasundaram5. 1. Professor (Biochemistry), Command Hospital (Air Force), Bengaluru, India. 2. Professor & Head, Department of Biochemistry, Armed Forces Medical College, Pune, India. 3. Assistant Professor, Subharti Medical College, SVSU, Meerut, UP, India. 4. Senior Advisor (Medicine & Hematology), Command Hospital (Central Command), Lucknow, India. 5. Senior Advisor (Pathology) & Hematopathologist, Army Hospital (R&R), Delhi Cantt, India.
Abstract
BACKGROUND: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are a spectrum of hematological malignancies with a multistep process of accumulated genetic and epigenetic alterations. DNA methylation is most extensively studied epigenetic alteration in malignancies. Recent research studies in the field have brought out translational implications of promoter methylation of tumor suppressor gene p15 in tumors. Therefore, we studied the role of DNA Methylation of p15 gene in AML and MDS. METHODS: The study was carried out in 41 consecutive AML/MDS cases reporting to hematological OPD of a tertiary care center along with 25 age and sex-matched healthy controls. The methylation status in the promoter region of the p15 gene was assessed by methylation-specific PCR (MSP) from blood samples after ethical approval and informed consent of the patients and controls. The association of methylation status was studied with clinical presentations, AML subtypes, and cytogenetics using Chi-square test/Fisher's exact test tools. RESULTS: A total of 41 cases included in the study comprised 33 cases of AML and 08 cases of MDS with an age range between 06 months and 82 years. Of the 41 cases, 29 revealed promoter methylation of the p15 gene, which compared to healthy controls was found statistically significant (p < 0.001). The methylation status did not significantly correlate with AML subtypes or the cytogenetic abnormalities detected in cases. CONCLUSION: The outcome of the study indicates p15 promoter DNA methylation in cases of AML and MDS may identify those individuals who might benefit from the targeted therapeutic approaches.
BACKGROUND: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are a spectrum of hematological malignancies with a multistep process of accumulated genetic and epigenetic alterations. DNA methylation is most extensively studied epigenetic alteration in malignancies. Recent research studies in the field have brought out translational implications of promoter methylation of tumor suppressor gene p15 in tumors. Therefore, we studied the role of DNA Methylation of p15 gene in AML and MDS. METHODS: The study was carried out in 41 consecutive AML/MDS cases reporting to hematological OPD of a tertiary care center along with 25 age and sex-matched healthy controls. The methylation status in the promoter region of the p15 gene was assessed by methylation-specific PCR (MSP) from blood samples after ethical approval and informed consent of the patients and controls. The association of methylation status was studied with clinical presentations, AML subtypes, and cytogenetics using Chi-square test/Fisher's exact test tools. RESULTS: A total of 41 cases included in the study comprised 33 cases of AML and 08 cases of MDS with an age range between 06 months and 82 years. Of the 41 cases, 29 revealed promoter methylation of the p15 gene, which compared to healthy controls was found statistically significant (p < 0.001). The methylation status did not significantly correlate with AML subtypes or the cytogenetic abnormalities detected in cases. CONCLUSION: The outcome of the study indicates p15 promoter DNA methylation in cases of AML and MDS may identify those individuals who might benefit from the targeted therapeutic approaches.
Authors: Sara Alvarez; Javier Suela; Ana Valencia; Agustín Fernández; Mark Wunderlich; Xabier Agirre; Felipe Prósper; José Ignacio Martín-Subero; Alba Maiques; Francesco Acquadro; Sandra Rodriguez Perales; María José Calasanz; Jose Roman-Gómez; Reiner Siebert; James C Mulloy; José Cervera; Miguel Angel Sanz; Manel Esteller; Juan C Cigudosa Journal: PLoS One Date: 2010-08-16 Impact factor: 3.240
Authors: P R Solomon; A K Munirajan; Nobuo Tsuchida; Kottampatti Muthukumarasamy; Andiappan Rathinavel; G S Selvam; G Shanmugam Journal: Indian J Med Res Date: 2008-01 Impact factor: 2.375