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Residual methylation of tumor suppressor gene promoters, RASSF6 and RASSF10, as novel biomarkers for minimal residual disease detection in adult acute lymphoblastic leukemia

  • Samareh Younesian
  • Sepideh Shahkarami
  • Parisa Ghaffari
  • Shaban Alizadeh
  • Roya Mehrasa
  • Seyed H. GhaffariEmail author
Original Article

Abstract

Aberrant promoter methylation of RASSF6 and RASSF10 occurs at a high frequency in acute lymphoblastic leukemia (ALL). Because of the complexity of the current minimal residual disease (MRD) detecting-methods, the DNA methylation status of the RASSF6 and RASSF10 genes could potentially become biomarkers for the assessment of MRD levels in ALL patients. The promoter methylation status of RASSF6 and RASSF10 was assessed by using methylation-specific PCR (MSP) in the DNA isolated from 280 peripheral blood (PB) samples taken at the time of diagnosis, day 14, 28, and from the subsequent 30-month follow-ups of 45 adult ALL patients. The relative methylation level obtained during the follow-ups by MSP was compared to the MRD results obtained by the amplification of IG/TCR clonal rearrangements using the allele-specific quantitative-PCR (ASO-PCR) assay. Frequently, RASSF6 was methylated in B-ALL, and RASSF10 was methylated in T-ALL. The applicability and accuracy of the assays were increased when these markers were combined (91.1% and 93.8%, respectively). When a cutoff was defined for the PCR-MRD level, results of the 30 months of MRD detection showed a significant correlation between the PCR and MSP techniques (r = 0.848; p < 0.001). Due to the high applicability, the non-invasiveness, and promising prospect of longitudinal assessment, the DNA methylation status of the RASSF6 and RASSF10 genes could be potential biomarkers for the assessment of residual disease in PB of patients with ALL.

Keywords

Minimal residual disease RASSF6 RASSF10 Acute lymphoblastic leukemia DNA hypermethylation Tumor suppressor gene 

Notes

Funding information

This study was supported by the Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. (Grant number: 95-01-36-31971).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati HospitalTehran University of Medical SciencesTehranIran
  2. 2.Department of Hematology, School of Allied Medical Sciences, International CampusTehran University of Medical SciencesTehranIran
  3. 3.Research Center for Immunodeficiencies, Children’s Medical CenterTehran University of Medical SciencesTehranIran
  4. 4.Department of Hematology, School of Allied Medical SciencesTehran University of Medical SciencesTehranIran

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