Genome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features.
نویسندگان
چکیده
Acute myeloid leukemia is a heterogeneous disease from the molecular and biologic standpoints, and even patients with a specific gene expression profile may present clinical and molecular heterogeneity. We studied the epigenetic profiles of a cohort of patients who shared a common gene expression profile but differed in that only half of them harbored mutations of the CEBPA locus, whereas the rest presented with silencing of this gene and coexpression of certain T-cell markers. DNA methylation studies revealed that these 2 groups of patients could be readily segregated in an unsupervised fashion based on their DNA methylation profiles alone. Furthermore, CEBPA silencing was associated with the presence of an aberrant DNA hypermethylation signature, which was not present in the CEBPA mutant group. This aberrant hypermethylation occurred more frequently at sites within CpG islands. CEBPA-silenced leukemias also displayed marked hypermethylation compared with normal CD34(+) hematopoietic cells, whereas CEBPA mutant cases showed only mild changes in DNA methylation compared with these normal progenitors. Biologically, CEBPA-silenced leukemias presented with a decreased response to myeloid growth factors in vitro.
منابع مشابه
MYELOID NEOPLASIA Genome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features
1Department of Medicine (Hematology Oncology Division), Weill Cornell Medical College, New York, NY; 2Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands; 3Department of Physiology and Biophysics and HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY; 4Department of Molecular...
متن کاملEpigenetic effects of decitabine on acute lymphoblastic and acute promyelocytic leukemia cells
Background: Decitabine (5-aza-2'-deoxycytidine, DAC) is a deoxycytidine analog currently used as an effective drug against myelodysplastic syndromes and acute myeloid leukemia. Although various studies have pointed out the epigenetic effects of this drug, its epigenetic mechanisms in different leukemic cell lines are not specified. In this lab trial study, possible epigenetic effects of decitab...
متن کاملClinical and Laboratory Findings of Cup-Like Nuclei in Blasts with FLT3 Mutation in Pediatric Acute Myeloid Leukemia: A Case Report
Biologically, Acute myeloid leukemia (AML) is highly heterogenous. AML with cup-like blast morphology variant has been reported to have important role in risk group stratification and treatment implications. In pediatric age group, this morphology and its clinical implication is rarely discussed. Although this morphology variant is not stated in World Health Organization (WHO) classification of...
متن کاملImmunophenotyping of Acute Leukemia in Northwestern Iran
The significance of immunophenotyping is growing day by day. Itprovides basic information in regard to classification and prognosisof acute leukemia which helps the management of patients. Thisstudy was conducted to Identify CD markers in leukemic patientsadmitted to Tabriz, in northwestern Iran. Immunophenotyping of 60patients with acute leukemia was determined. Patients with acutemyelogenous ...
متن کاملIntravenous anti-D treatment for immune thrombocytopenic purpura.
the TCR d gene rearrangements in AML show the same pattern as those in T-ALL,4 and occur more frequently in immature AML3,6 or in lymphoid antigen–(CD2, CD4, or CD7) positive (Ly1) AML.4 Because myeloid/NK cell precursor acute leukemia can be recognized as immature AML or Ly1 AML, the existence of the Dd2-Jd1 pattern of TCR d gene rearrangement in myeloid/NK cell precursor acute leukemia is con...
متن کاملذخیره 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 ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Blood
دوره 113 12 شماره
صفحات -
تاریخ انتشار 2009