TREATMENT OF SICKLE-CELL-ANEMIA WITH 5-AZACYTIDINE RESULTS IN INCREASED FETAL HEMOGLOBIN PRODUCTION AND IS ASSOCIATED WITH NONRANDOM HYPOMETHYLATION OF DNA AROUND THE GAMMA-DELTA-BETA-GLOBIN GENE-COMPLEX
TREATMENT OF SICKLE-CELL-ANEMIA WITH 5-AZACYTIDINE RESULTS IN INCREASED FETAL HEMOGLOBIN PRODUCTION AND IS ASSOCIATED WITH NONRANDOM HYPOMETHYLATION OF DNA AROUND THE GAMMA-DELTA-BETA-GLOBIN GENE-COMPLEX
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DOI：
10.1073/pnas.80.15.4842
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发表时间：
1983-01-01
期刊：
影响因子：
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通讯作者：
BOYER, S
中科院分区：
文献类型：
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作者：
CHARACHE, S;DOVER, G;BOYER, S
在一名接受5-氮杂胞苷治疗的镰状细胞性贫血患者中观察到胎儿血红蛋白（HbF）产生增加。四个疗程中的每一个疗程都导致含HbF的网织红细胞（F网织红细胞）和含HbF的红细胞（F细胞）的百分比快速且延长的增加。外周血中HbF的百分比从1.8%上升到8.9%。HbF产生的增加伴随着外周血血红蛋白浓度从8 g/dl增加到12 g/dl以及平均红细胞体积的增加。用5-氮杂胞苷治疗导致从外周血和骨髓中分离的总基因组和Y染色体特异性DNA片段的低甲基化。在γ-δ-β-珠蛋白基因复合体周围的15个限制性内切酶位点中，只有2个变成低甲基化：一个是γ G基因5'端的107个碱基，另一个是γ A珠蛋白基因5'端的107个碱基。
Increased production of fetal hemoglobin (HbF) was observed in a patient with sickle cell anemia treated with 5-azacytidine. Each of four courses of therapy resulted in a rapid and prolonged increase in the percentage of HbF containing reticulocytes (F reticulocytes) and HbF containing erythrocytes (F cells). The percentage of HbF in peripheral blood rose from 1.8 to 8.9%. The rise in HbF production was accompanied by an increase in peripheral blood hemoglobin concentration from 8 to 12 g/dl and an increase in mean erythrocyte volume. Treatment with 5-azacytidine resulted in hypomethylation of total genomic and a Y-chromosome-specific DNA fragment isolated from both peripheral blood and bone marrow. Of 15 restriction enzyme sites around the gamma-delta-beta-globin gene complex, only 2 became hypomethylated: one 107 bases 5' to the gamma G and the other 107 bases 5' to the gamma A globin genes.