From the Istituto di Ematologia, Università Cattolica S. Cuore, Rome, Italy.
Death-associated protein kinase (DAP-kinase), a proapoptotic serine/threonine kinase, is a candidate tumor suppressor gene. We studied the methylation status of DAP-kinase of 194 bone marrow samples from 160 patients with acute myeloid leukemia (AML) and 34 with a myelodysplastic syndrome (MDS) at the time of initial diagnosis by polymerase chain reaction (PCR). Hypermethylation of DAP-kinase was present in 27.5% (44 of 160) of AML and in 47% (16 of 34) of MDS specimens and significantly correlated to loss of DAP-kinase expression (P = .008). It was significantly more frequent in AML secondary to therapy for other malignancies (s-AML; 14 of 29, 48.3%), as compared to de novo AML (30 of 131, 22.9%, P = .01). DAP-kinase hypermethylation in AML was associated with myelodysplastic changes in the bone marrow at the time of the initial diagnosis (P = .002) and with the presence of cytogenetic abnormalities (P = .02). Alteration in the apoptotic response due to the loss of DAP-kinase function may be an early event in the transformation pathway to secondary leukemia via myelodysplasia.
Thrombopoietin initiates demethylation-based transcription of GP6 during megakaryocyte differentiation
Role of Protein Methylation in Regulation of Transcription
A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group
A picture (in the microscope) is worth a thousand words
Added challenges to gene therapy—immune responses in the setting of myeloablation
Alphastatin a 24–amino acid fragment of human fibrinogen is a potent new inhibitor of activated endothelial cells in vitro and in vivo
Antibodies against lepirudin are polyspecific and recognize epitopes on bivalirudin
BAFF and related proteins: a new therapeutic target for B-cell malignancies
CD44-hyaluronic acid interactions mediate shear-resistant binding of lymphocytes to dermal endothelium in acute cutaneous GVHD
Clinical course of patients with WASP gene mutations