癌基因c-erbB在骨髓增生异常综合征(MDS)骨髓细胞中的表达及其意义

SIGNIFICANCE OF c-erbB EXPRESSION IN MARROW CELLS OF MYELODYSPLASTIC SYNDROME (MDS) PATIENTS

采用生物素标记探针原位杂交(ISH)对MDS13例、急非淋(ANLL)10例和良性血液病8例,共31例患者骨髓细胞c-erbB表达进行了观察,同时对c-myc表达作了比较,发现8/13例MDSc-erbB mRNA过高表达,10/13例MDSc-myc mRNA过高表达;在10例ANLL病人中,仅1例c-erbB mRNA高表达,7例c-myc mRNA高表达;8例良性血液病两种癌基因均无表达,1例在2月内由RA发展到RAEB-T患者其c-erbB和c-myc表达明显增强。用ISH发现癌基因过度表达比临床常规形态学确诊提前8周,提示c-erbB和c-myc转录增强对MDS急剧演变有预后意义,c-erbB参与MDS发生与发展过程。

Myelodysplastic syndrome (MDS) is the abnormal clonal proliferation on stem cell level. Point mutation and overexpression of N-ras and c-myc genes were discovered. However, only a few reports concerned c-erbB gene in MDS. In our laboratory, biotinated cDNA probes and SA-AP detected system(BRL) were used for DNA-mRNA in situ hybridization in 31 cases with MDS, ANLL or benign hemopathy. The results showed that 4/8 RA and 3/5 RAEB exhibited c-erbB mRNA overexpression, while 6/8 RA and 4/5 RAEB exhibited c-myc mRNA overexpression. In contrast, it could not be detected for 8 cases of benign hemopathy (5 IDA, 3 ITP). However, overexpression was found only in 1 / 10 ANLL cases for c-erbB mRNA, in 7 / 10 ANLL cases for c-wjcmRNA. In addition, progressive overexpression of this two oncogenes was found in one case of MDS, developing from RA to RAEB-T in two months. The positive rate of c-erbB mRNA increased from 0% to 42% and c-myc mRNA increased from 15% to 68%, respectively. Interestingly, both oncogenes were progressively overexpressed 8 weeks earlier than diagnosis of RAEB-T by routine morphological methods. It was suggested that the increasing transcription level of c-erbB and c-myc might be significant for prognosis of MDS.