Contributions
Abstract: PB2257
Type: Publication Only
Background
Aberrant promoter methylation is an epigenetic mechanism for silencing tumor suppressor genes (TSG), and is also a biomarker for early cancer diagnosis and prognosis prediction. HLS5 belongs to the RBCC (Ring-finger, B-box, coiled-coil) family, a family of tumor suppressive genes including Pm, Tif1-α,Herf and Rfp, it has been reported to regulate erythroid differentiation, to be activated during the conversion of J2E erythroleukemic cells to monocytoid cells, and assumed to be a tumor supressor.However, the role of HLS5 in acute myeloid leukemia and myeloproliferative neoplasms has never been explored.
Aims
the role of HLS5 in acute myeloid leukemia and myeloproliferative neoplasms
Methods
Bone marrow of 35 de novo AML-M2 , 20 de novo AML-M5 and 68 JAK2/V617F mutation positive MPN patients were collected, the mononucleated cells separated, RNA extracted and the HLS5 expression level detected using real-time quantitative PCR and MSP. SPSS 16.0 used for data analysis.
Results
We identified HLS5 as a functional tumor suppressor gene frequently methylated in multiple myeloid neoplasms. We further uncovered HLS5 as one of the up regulated genes in myeloid neoplasm cell lines after pharmacologic demethylation with 5 aza 2’ deoxycytidine (Aza). Methylation of HLS5 was detected in most acute myeloid leukemia cell lines, including KG1, Kasumi-1, U937, THP, HL60 cell lines and JAK2/V617F mutation positive cells. Aza treatment led to HLS5 promoter demethylation and transcriptional reactivation in silenced cell lines, indicating a methylation mediated silencing. Aberrant methylation was further detected in 40% (14/35) AML-M2, 60% (12/20) AML-M5 and 60-80% of various types of JAK2/V617F mutation positive MPN, but not in any normal PBMC sample, and is thus tumor specific. Moreover, HLS5 methylation was detected in 3/10 (30%) serum samples from MF patients.
Conclusion
Our results indicate that HLS5 methylation is a frequent event in multiple myeloid neoplasms, especially for AML and MPN, but the exact mechanism needs further investigation.
Session topic: 15. Myeloproliferative neoplasms – Biology & Translational Research
Keyword(s): AML, Epigenetic, Myeloproliferative disorder
Abstract: PB2257
Type: Publication Only
Background
Aberrant promoter methylation is an epigenetic mechanism for silencing tumor suppressor genes (TSG), and is also a biomarker for early cancer diagnosis and prognosis prediction. HLS5 belongs to the RBCC (Ring-finger, B-box, coiled-coil) family, a family of tumor suppressive genes including Pm, Tif1-α,Herf and Rfp, it has been reported to regulate erythroid differentiation, to be activated during the conversion of J2E erythroleukemic cells to monocytoid cells, and assumed to be a tumor supressor.However, the role of HLS5 in acute myeloid leukemia and myeloproliferative neoplasms has never been explored.
Aims
the role of HLS5 in acute myeloid leukemia and myeloproliferative neoplasms
Methods
Bone marrow of 35 de novo AML-M2 , 20 de novo AML-M5 and 68 JAK2/V617F mutation positive MPN patients were collected, the mononucleated cells separated, RNA extracted and the HLS5 expression level detected using real-time quantitative PCR and MSP. SPSS 16.0 used for data analysis.
Results
We identified HLS5 as a functional tumor suppressor gene frequently methylated in multiple myeloid neoplasms. We further uncovered HLS5 as one of the up regulated genes in myeloid neoplasm cell lines after pharmacologic demethylation with 5 aza 2’ deoxycytidine (Aza). Methylation of HLS5 was detected in most acute myeloid leukemia cell lines, including KG1, Kasumi-1, U937, THP, HL60 cell lines and JAK2/V617F mutation positive cells. Aza treatment led to HLS5 promoter demethylation and transcriptional reactivation in silenced cell lines, indicating a methylation mediated silencing. Aberrant methylation was further detected in 40% (14/35) AML-M2, 60% (12/20) AML-M5 and 60-80% of various types of JAK2/V617F mutation positive MPN, but not in any normal PBMC sample, and is thus tumor specific. Moreover, HLS5 methylation was detected in 3/10 (30%) serum samples from MF patients.
Conclusion
Our results indicate that HLS5 methylation is a frequent event in multiple myeloid neoplasms, especially for AML and MPN, but the exact mechanism needs further investigation.
Session topic: 15. Myeloproliferative neoplasms – Biology & Translational Research
Keyword(s): AML, Epigenetic, Myeloproliferative disorder