ABSTRACT
The Dickkopf-1 (DKK1) gene product is an extracellular Wnt inhibitor. Hypermethylation of the DKK1 promoter results in transcriptional silencing and may play an important role in cancer development. Here, we investigated hypermethylation of the DKK1 promoter in patients with acute myeloid leukaemia (AML), especially core-binding factor (CBF) leukaemia. The methylation status of DKK1 was analysed using methylation-specific polymerase chain reaction in 47 patients with AML. DKK1 methylation was found in 14 (29.8%) patients, and more frequently in those with CBF leukaemia (6 of 12 patients), than in those with acute promyelocytic leukaemia (APL) (0 of 6 patients) (P = 0.03). In contrast, Wnt inhibitory factor-1 methylation was found in APL (4 of 6 patients) but not in CBF leukaemia (0 of 12 patients) (P = 0.001). Multivariate analyses suggested that DKK1 methylation was a risk factor for poorer overall survival. Sequential analysis using four paired samples obtained at diagnosis and relapse suggested that DKK1 methylation was involved in the progression of leukaemia. Therefore, DKK1 methylation may be involved in leukaemogenesis, especially in CBF leukaemia, and may be a useful prognostic marker in AML.
Subject(s)
Biomarkers, Tumor/genetics , DNA Methylation , Intercellular Signaling Peptides and Proteins/genetics , Leukemia, Myeloid/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Bone Marrow Cells/metabolism , Core Binding Factors/metabolism , DNA, Neoplasm/genetics , Disease Progression , Female , Humans , Intercellular Signaling Peptides and Proteins/metabolism , Leukemia, Myeloid/metabolism , Male , Middle Aged , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Prognosis , Promoter Regions, Genetic/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Survival Analysis , Tumor Cells, CulturedABSTRACT
Mutations in the fms-like tyrosine kinase 3 (FLT3) gene containing an internal tandem duplication (FLT3/ITD) or mutations in the nucleophosmin 1 gene (NPM1) are thought to be prognostic indicators in acute myeloid leukemia (AML). Previous studies suggested that FLT3/ITD mutation indicates a poor prognosis and that NPM1 mutation indicates a more favorable one, but these studies were often performed with selected patient populations. We investigated the clinical significance of these mutations at our institution with an unselected group of patients with newly diagnosed AML. This group included patients > or =60 years old and those with a poor performance status. Using polymerase chain reaction and sequencing analyses, we detected FLT3/ITD mutations in 12 patients (20.0%) and NPM1 mutations in 7 patients (11.7%) among a group of 60 patients. There was a nonsignificant trend for FLT3/ITD mutation to be associated with a poorer predicted overall survival (OS) probability in this population. In contrast, OS was significantly higher in patients with wild-type NPM1 than in patients with NPM1 mutation, both for all AML patients and for AML patients with a normal karyotype. In this general and unselected AML patient population, NPM1 mutation was not a prognostic indicator of a favorable outcome.
Subject(s)
Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Mutation , Nuclear Proteins/genetics , fms-Like Tyrosine Kinase 3/genetics , Adolescent , Adult , Aged , Aged, 80 and over , DNA Mutational Analysis , Disease-Free Survival , Female , Humans , Male , Middle Aged , Nucleophosmin , Polymerase Chain Reaction , Predictive Value of Tests , Survival RateABSTRACT
Lung involvement is rare in Waldenström macroglobulinemia (WM). We encountered a male patient with WM who complained of breathlessness. Chest X-ray revealed diffuse infiltrative shadow throughout the both lungs. Transbronchial biopsy showed infiltration of atypical plasmacytoid lymphocytes and non-caseating granuloma. We treated the patients with fludarabine phosphate, and both his symptom and X-ray findings were then improved. To our knowledge, this is the first case showing non-caseating granuloma with lung involvement of WM. We discuss a mechanism of non-caseating granuloma formation in this case.
Subject(s)
Plasma Cell Granuloma, Pulmonary/etiology , Waldenstrom Macroglobulinemia/complications , Antimetabolites, Antineoplastic/therapeutic use , Humans , Male , Middle Aged , Plasma Cell Granuloma, Pulmonary/diagnostic imaging , Plasma Cell Granuloma, Pulmonary/drug therapy , Radiography , Treatment Outcome , Vidarabine Phosphate/analogs & derivatives , Vidarabine Phosphate/therapeutic use , Waldenstrom Macroglobulinemia/diagnostic imaging , Waldenstrom Macroglobulinemia/drug therapyABSTRACT
OBJECTIVE: To evaluate intestinal lesions in Burkitt lymphoma. METHODS: Ultrasonography was used in the initial evaluation of 6 Japanese patients with intestinal Burkitt lymphoma. RESULTS: Ultrasonography revealed marked wall thickening of the colon from the cecum through either the ascending or the transverse colon, which led to a target sign (4 cases) or a pseudokidney sign (2 cases). The target sign histopathologically corresponded to invagination of an occult tumor of the cecum into the ascending colon. Wall thickening of the colon when associated with a target or pseudokidney sign corresponded to marked lymph edema or a diffuse infiltration of Burkitt lymphoma cells into the intramural layers, respectively CONCLUSIONS: Ultrasonography provides useful information in the initial evaluation of intestinal lesions with distinctive histopathologic characteristics in Burkitt lymphoma.
