Extensive intra- and interindividual heterogeneity of p15INK4B methylation in acute myeloid leukemia.

نویسندگان

  • A Aggerholm
  • P Guldberg
  • M Hokland
  • P Hokland
چکیده

Silencing of the cyclin-dependent kinase inhibitor gene p15INK4B by cytosine methylation of the promoter region has been associated with some types of hematological malignancy. To study in detail the patterns of p15INK4B methylation in patients with acute myeloid leukemia, we adopted a novel approach based on PCR amplification of bisulfite-treated DNA followed by resolution of differentially methylated sequences by denaturing gradient gel electrophoresis. This method visually displays the degree and heterogeneity of DNA methylation and enables the isolation and characterization of distinct clonotypic epigenotypes. A surprisingly high degree of intra- and interindividual heterogeneity of p15INK4B methylation was observed in the 65 acute myeloid leukemia patients examined. Methylation was detected in 46 (71%) of the patients and was observed more frequently in the French-American-British subtypes M1/M2 than in M4/M5 (P < 0.025). Examination of the same panel of samples using a highly sensitive methylation-specific PCR method showed methylated p15INK4B alleles in 61 (94%) of the samples. We present evidence that the higher frequency of p15INK4B methylation determined by methylation-specific PCR may, at least in part, be due to the presence of a small fraction of p15INK4B-methylated lymphocytes in normal blood.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Extensive Intra- and Interindividual Heterogeneity of p15 Methylation in Acute Myeloid Leukemia

Silencing of the cyclin-dependent kinase inhibitor gene p15 by cytosine methylation of the promoter region has been associated with some types of hematological malignancy. To study in detail the patterns of p15 methylation in patients with acute myeloid leukemia, we adopted a novel approach based on PCR amplification of bisulfite-treated DNA followed by resolution of differentially methylated s...

متن کامل

Methylation Status of SOX17 and RUNX3 Genes in Acute Leukemia

Background: Several studies have examined the presence of DNA methylation of CpG islands in leukemia. Methylation of SOX17 and RUNX3 genes may play a role in leukemogenesis through silencing tumor suppressor genes. We investigated the methylation status of SOX17 and RUNX3 genes in patients with acute leukemia.    Methods: In this case-control study, peripheral blood samples from 100 AML and 10...

متن کامل

Myeloid-specific inactivation of p15Ink4b results in monocytosis and predisposition to myeloid leukemia.

Inactivation of p15INK4b, an inhibitor of cyclin-dependent kinases, through DNA methylation is one of the most common epigenetic abnormalities in myeloid leukemia. Although this suggests a key role for this protein in myeloid disease suppression, experimental evidence to support this has not been reported. To address whether this event is critical for premalignant myeloid disorders and leukemia...

متن کامل

Geographic Heterogeneity of the AML1-ETO Fusion Gene in Iranian Patients with Acute Myeloid Leukemia

Background: The human AML1 gene, located on chromosome 21, can be fused to the AML1- eight-twenty-one (ETO) oncoprotein on chromosome eight, resulting in a t(8;21)(q22;q22) translocation. Acute myeloid leukemia (AML) associated with this translocation is considered a distinct AML with a favorable prognosis. Due to the various incidences of the translocation, which is associated with geographic ...

متن کامل

The tumor suppressor p15Ink4b regulates the differentiation and maturation of conventional dendritic cells.

The tumor suppressor p15Ink4b is frequently inactivated by methylation in acute myeloid leukemia and premalignant myeloid disorders. Dendritic cells (DCs) as potent APCs play critical regulatory roles in antileukemic immune responses. In the present study, we investigated whether p15Ink4b can function as modulator of DC development. The expression of p15Ink4b is induced strongly during differen...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Cancer research

دوره 59 2  شماره 

صفحات  -

تاریخ انتشار 1999