内源性逆病毒癌基因V-erbB突变与白血病发生

目的：证明鸡原始红细胞增多症逆病毒癌基因V—erbB在人类白血病和骨髓增生异常综合征(MDS)急者基因组内的存在。方法：应用V—erbB PCR，V—erbB寡核苷酸(Oligo)原位杂交技术和PCR产物DNA测序，对84例MDS、可疑MDS和49例其他相关血液病进行检到。结果：2例患者骨殖细胞基因组内均存在V—erbB亚基因片段，同源性占99．5％，它们具有相同的限制性酶勿位点，因此可以在Southern印迹杂交条件下发生骨髓细胞C—erbB重排和重排／扩增。白前P1P2PCR产物有420bp，P1P3产物有650bp，而白血病(AL—M4)P1P2PCR产物仅390bp，P1P3PCR因P3无模板序列而无结果。提示从白前发展为白血病，可能发生V—erbB亚基因序列的缺失，即缺失突变。结论：大鼠和人白血病和食管癌等可能均起源于其基因组内存在V—erbB亚基因及其缺失突变。白血病发病中除了上述病因以外，骨髓细胞染色体不稳定性可能起协同作用。

V-erbB MUTATION OF HUMAN ENDOGENOUS RETROVIRUS ONCOGENE AND LEUKEMIA OCCURENCE

Objective:The objective of this paper is in detecting the endogenous avian erythrob- lastosis retrovirus oncogenes,V- erb B in genome of patients with leukem ia.Methods:V - erb B PCR and its products sequencing and V- erb B oligodeoxynucleotides in situ hybridization techniques.Results: The results showed the significance in diagnosis of MDS and developm entof leukem ia.This was sup- ported by results of chrom osome examinations and following up of cases.In two patients(one with AML- M4 in a fam ily with7AML,another with preleukemia in a fam ily with 5 AL L) the V- erb B PCR and sequencing of its products were performed by using prim ers P1 P2 and P1 P3and BM cell DNA.The results were analysed homologically in com puter with Gene Runner software.Their same sequence of P1 P2 PCR product was found to be same P1 P2 sequence of V- erb B (V - erb B subgene,ho- mology 99.5 % ) .The deletion of sequence was also found in AML- M4 ,because the sequence of preleukemia is6 5 0 bp and one of leukemia is only390 bp.This suggests that deletion- mutation occurs in development of preleukemia into leukem ia.Conclusion:Since human and rat leukemia and MDS, and also esophagical cancer have same rearrangement/am plification of C- erb B and the V- erb B sub- gene exists in their genome,human cancers m ay have com mon origin of V - erb B subgene and its dele- tion/mutation.Its antigene ODN phosphotioate can reverse human MDS and premalignancy.In leuko- mogenesis the chromosome unstability m ay play cooperative role.