Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome

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Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome

Grövdal, Michael (författare): Grövdal, M., Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden

Khan, Rasheed (författare): Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden

Aggerholm, Anni (författare): Karolinska Institutet,Department of Haematology, Aarhus University Hospital, Aarhus, Denmark,Department of Haematology, Sahlgrenska University Hospital, Göteborg, Sweden,Department of Pathology, Radiumhemmet, Karolinska University Hospital, Solna, Stockholm, Sweden

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Antunovic, Petar (författare): Linköpings universitet,Hälsouniversitetet,Institutionen för biomedicin och kirurgi

Astermark, Jan (författare): Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine,Department for Haematology and Coagulation Disorders, Malmö University Hospital, Malmö, Sweden

Bernell, Per (författare): Division of Haematology, Department of Medicine, Karolinska University Hospital, Solna, Stockholm, Sweden

Engström, Lena-Maria (författare): Engström, L.-M., Medical Clinic, Department of Haematology, University Hospital of Norrland, Umeå, Sweden

Kjeldsen, Lars (författare): Department of Haematology, Rigshospitalet, Copenhagen, Denmark

Linder, Olle (författare): Department of Medicine, Örebro University Hospital, Örebro, Sweden

Nilsson, Lars (författare): Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Haematopoietic Stem Cell Laboratory, Department of Haematology, Lund University Hospital, Lund, Sweden

Olsson, Anna (författare)

Wallvik, Jonas (författare): Division of Haematology, Department of Medicine, Sundsvall Hospital, Sundsvall, Sweden

Tangen, Jon Magnus (författare): Department of Haematology, Ullevål University Hospital, Oslo, Norway

Öberg, Gunnar (författare): Uppsala universitet,Institutionen för medicinska vetenskaper,Blodsjukdomar,Öberg, G., Department of Haematology, Uppsala Academic Hospital, Uppsala, Sweden

Jacobsen, Sten Eirik (författare): Haematopoietic Stem Cell Laboratory, Department of Haematology, Lund University Hospital, Lund, Sweden

Hokland, Peter (författare): Department of Haematology, Aarhus University Hospital, Aarhus, Denmark

Porwit, Anna (författare)

Hellström-Lindberg, Eva (författare): Karolinska Institutet,Hellström-Lindberg, E., Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Huddinge, SE-14186 Stockholm, Sweden

Engstroem, LV (författare)

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Grövdal, M, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden (creator_code:org_t)

2007
2007
Engelska.
Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:23, s. 7107-7112

Relaterad länk:: http://dx.doi.org/10... (free); visa fler...; https://urn.kb.se/re...; https://doi.org/10.1...; http://kipublication...; https://lup.lub.lu.s...; https://urn.kb.se/re...; visa färre...

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PURPOSE: Promoter hypermethylation of, for example, tumor-suppressor genes, is considered to be an important step in cancerogenesis and a negative risk factor for survival in patients with myelodysplastic syndromes (MDS); however, its role for response to therapy has not been determined. This study was designed to assess the effect of methylation status on the outcome of conventional induction chemotherapy. EXPERIMENTAL DESIGN: Sixty patients with high-risk MDS or acute myeloid leukemia following MDS were treated with standard doses of daunorubicin and 1-beta-d-arabinofuranosylcytosine. Standard prognostic variables and methylation status of the P15(ink4b) (P15), E-cadherin (CDH), and hypermethylated in cancer 1 (HIC) genes were analyzed before treatment. RESULTS: Forty percent of the patients achieved complete remission (CR). CR rate was lower in patients with high WBC counts (P = 0.03) and high CD34 expression on bone marrow cells (P = 0.02). Whereas P15 status alone was not significantly associated with CR rate (P = 0.25), no patient with hypermethylation of all three genes achieved CR (P = 0.03). Moreover, patients with CDH methylation showed a significantly lower CR rate (P = 0.008), and CDH methylation retained its prognostic value also in the multivariate analysis. Hypermethylation was associated with increased CD34 expression, but not with other known predictive factors for response, such as cytogenetic profile. CONCLUSIONS: We show for the first time a significant effect of methylation status on the outcome of conventional chemotherapy in high-risk MDS and acute myelogenous leukemia following MDS. Provided confirmed in an independent study, our results should be used as a basis for therapeutic decision-making in this patient group.

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

Artiklar i publikationen: Clinical Cancer ...

Av lärosätet: Uppsala universitet; Karolinska Institutet; Lunds universitet; Linköpings universitet

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Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome

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