ABSTRACT
Numerous genetic abnormalities which can not be identified by cytogenetic detection (e.g., gene mutations, gene expression abnormalities) have been gradually found, which means that the further molecular classification of AML (acute myeloid leukemia) with distinctive prognosis have arrived. For example, mutations of the transcription factor (CCAAT enhancer binding factor alpha, C/EBPalpha) or nucleophosmin-1 (NPM1) may predict better prognosis, whereas partial tandem duplications of the MLL gene (MLL-PTD), internal tandem duplications of FLT3 (FLT3-ITD) or mutations of WT1 gene confer worse prognosis. This review focuses on the features and relationship of these genetic abnormalities, as well as their influence on the prognosis of AML.
Subject(s)
Humans , Leukemia, Myeloid, Acute , Diagnosis , Genetics , PrognosisABSTRACT
This study was purposed to explore the expression of glucosylceramide synthase (GCS) in human leukemia cells and its relationship with multidrug resistance. RT-PCR was used to analyze peripheral blood samples from 53 leukemia patients with multidrug resistance/non-resistance, and to detect the expression level of GCS gene in HL-60 cells and HL-60/ADR cells, the expression level was compared with the level of mdr-1. The expressions of GCS protein and P-gp protein in HL-60 cells and HL-60/ADR cells were assayed by Western blot analysis. The results showed that the relative optical density ratio of GCS gene amplified bands in samples of leukemia patients with drug-resistance was significantly higher than that in samples of leukemia patients with drug non-resistance group (P < 0.05), meanwhile the significant enhancement of optical density value of GCS gene amplified bands accompanied by high expression of mdr-1 gene. Their correlation showed positive (P < 0.01, r = 0.6). The GCS mRNA and protein were overexpressed in HL-60/ADR cells, and their expression levels were obviously higher than that in HL-60 cells, meanwhile the expression of mdr-1 mRNA and P-gp also significantly increased in HL-60/ADR cells. It is concluded that the high level of GCS in leukemia patients possibly is associated with multidrug resistance of leukemia cells.