石茵, 向谱, 黄昊, 等. 三氧化二砷治疗慢性粒细胞性白血病的实验与临床研究[J]. 临床血液学杂志, 2017, 30(1): 26-30. doi: 10.13201/j.issn.1004-2806.2017.01.007
引用本文:
石茵, 向谱, 黄昊, 等. 三氧化二砷治疗慢性粒细胞性白血病的实验与临床研究[J]. 临床血液学杂志, 2017, 30(1): 26-30.
doi:
10.13201/j.issn.1004-2806.2017.01.007
SHI Yin, XIANG Pu, HUANG Hao, et al. Clinical and experimental studies on arsenic trioxide in the treatment of chronic myeloid leukemia[J]. J Clin Hematol, 2017, 30(1): 26-30. doi: 10.13201/j.issn.1004-2806.2017.01.007
Citation:
SHI Yin, XIANG Pu, HUANG Hao, et al. Clinical and experimental studies on arsenic trioxide in the treatment of chronic myeloid leukemia[J]. J Clin Hematol, 2017, 30(1): 26-30.
doi:
10.13201/j.issn.1004-2806.2017.01.007
目的:
观察三氧化二砷(As
2
O
3
)对免疫表型FIK1
+
CD34
-
的慢性粒细胞白血病(CML)干细胞增殖的影响,并初步探讨As
2
O
3
使CML患者能中断酪氨酸激酶抑制剂治疗的可行性。
方法:
分离CML患者骨髓细胞中FIK1
+
CD34
-
CML干细胞,检测As
2
O
3
对其细胞周期、凋亡及P53基因表达的影响,并观察应用伊马替尼后已获得完全细胞遗传学缓解的CML患者,单用As
2
O
3
注射液6周期后,其疗效及不良反应。
结果:
As
2
O
3
能抑制免疫表型为FIK1
+
CD34
-
的CML干细胞增殖(
P
<0.05),可使其G0/G1期增加,S期降低,并可诱导凋亡。FIK1
+
CD34
-
CML干细胞经适当浓度的As
2
O
3
处理后,P53基因表达可显著提高。6例患者单用As
2
O
3
仍保持完全细胞遗传学缓解,且不良反应轻微,经对症处理后均可缓解。
结论:
As
2
O
3
对CML患者的治疗有一定效果,且无明显毒副作用,为使CML患者能中断酪氨酸激酶抑制剂的治疗提供了新的研究方向。
白血病,粒细胞,慢性
三氧化二砷
Abstract:
Objective:
To observe the effect of ATO on the proliferation of FIK1
+
CD34
-
chronic myeloid leukemia (CML) stem cells,and determine whether ATO alone could maintain remissions achieved by a prior therapy with tyrosine kinase inhibitor.
Method:
We isolated FIK1
+
CD34
-
CML stem cells from the bone marrow of newly diagnosed CML and analyzed the effect of ATO on cell cycle,apoptosis and the gene expression of P53 in FIK1
+
CD34
-
CML stem cells.We observed remission status and adverse events of ATO used alone in 6 patients who had been pretreated with imatinib and got complete cytogenetic response.
Result:
ATO could inhibit the proliferation of FIK1
+
CD34
-
CML stem cells.After treatment with ATO,the cells in G0/G1 phase increased and those in S phase decreased.Furthermore,ATO could induce apoptosis of FIK1
+
CD34
-
CML stem cells and increase remarkably the expression of P53 gene.After the application of ATO for 6 cycles,all the 6 patients remained complete cytogenetic remission.Furthermore,all the adverse events were modest and responded to symptomatic treatment.
Conclusion:
Treatment with ATO in patients with CML may have a good result without obvious ATO-related toxicities,and it gives a new way to cure CML without tyrosine kinase inhibitor.
Key words:
chronic myeloid leukemia
arsenic trioxide
chemotherapy
preliminary study