THE ANTILEUKEMIC ACTIVITY OF 5-AZA-2 DEOXYCYTIDINE (AZA-DC) IN PATIENTS WITH RELAPSED AND RESISTANT LEUKEMIA

被引:67
作者
RICHEL, DJ
COLLY, LP
KLUINNELEMANS, JC
WILLEMZE, R
机构
[1] Department of Haematology, University Medical Centre, Leiden
关键词
5-AZA-2'-DEOXYCYTIDINE; LEUKEMIA; DNA; DIFFERENTIATION; INHIBITION; INDUCTION; CYTOSINE; CELLS; MICE;
D O I
10.1038/bjc.1991.258
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In the present study we demonstrate that Aza-dC in combination with Amsacrine has major antileukaemic properties in patients who have not already received extensive Ara-C therapy. Eight out of 11 patients in their first relapse of acute leukaemia achieved complete remission. Cross resistance between Ara-C and Aza-dC was revealed by the lack of antileukaemic activity in five patients with with Ara-C resistant leukaemia. Combination therapy with Aza-dC/Ams-acrine induced a considerable period of a granulo-cytopenia (28-35 days), while the toxic effect on erythro- and megakaryopoiesis was comparable to that reported for high dose Ara-C/Amsacrine chemotherapy. Remarkable is the long disappearance time for leukaemic blast cells in bone marrow, i.e. 3-5 weeks in some cases. Analysis of cell membrane markers showed a loss of the early differentiation antigens CD34 and CD33 from leukaemic bone marrow cells after 7 days of Aza-dC treatment, which is suggestive of leukaemic cell differentiation. In the small group of patients tested for DNA hypomethylation no association existed between the degree of hypomethylation and clinical response. Non-haematologic side effects were considerable in patients receiving the highest dosages of Aza-dC and consisted of severe, although usually reversible, gastrointestinal and neurological complications. In comparison with Ara-C, Aza-dC causes less nausea and vomiting and is therefore better tolerated.
引用
收藏
页码:144 / 148
页数:5
相关论文
共 50 条
[41]   Reactivation of development-related genes by the DNA methylation inhibitor 5-Aza-2′-deoxycytidine in chicken embryo fibroblasts [J].
Chen, Shihao ;
Hu, Xuming ;
Zhu, Wenqi ;
Jia, Chongxin ;
Han, Xiao ;
Yuan, Junting ;
Sun, Zhen ;
Yang, Zhe ;
Geng, Tuoyu ;
Cui, Hengmi .
POULTRY SCIENCE, 2017, 96 (04) :1007-1014
[42]   Altered Hox gene expression and cellular pathogenesis of 5-aza-2′-deoxycytidine-induced murine hindlimb dysmorphogenesis [J].
Branch, S ;
Henry-Sam, G .
TOXICOLOGIC PATHOLOGY, 2001, 29 (05) :501-506
[43]   Targeting the Unique Methylation Pattern of Androgen Receptor (AR) Promoter in Prostate Stem/Progenitor Cells with 5-Aza-2′-deoxycytidine (5-AZA) Leads to Suppressed Prostate Tumorigenesis [J].
Tian, Jing ;
Lee, Soo Ok ;
Liang, Liang ;
Luo, Jie ;
Huang, Chiung-Kuei ;
Li, Lei ;
Niu, Yuanjie ;
Chang, Chawnshang .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (47) :39954-39966
[44]   Validating the Demethylating Effects of 5-aza-2′-deoxycytidine in Insects Requires a Whole-Genome Approach (A Reply to Ellers et al.) [J].
Cook, Nicola ;
Parker, Darren J. ;
Tauber, Eran ;
Pannebakker, Bart A. ;
Shuker, David M. .
AMERICAN NATURALIST, 2019, 194 (03) :432-438
[45]   Differential Induction of Apoptosis and Senescence by the DNA Methyltransferase Inhibitors 5-Azacytidine and 5-Aza-2′-Deoxycytidine in Solid Tumor Cells [J].
Venturelli, Sascha ;
Berger, Alexander ;
Weiland, Timo ;
Essmann, Frank ;
Waibel, Michaela ;
Nuebling, Tina ;
Haecker, Sabine ;
Schenk, Martin ;
Schulze-Osthoff, Klaus ;
Salih, Helmut R. ;
Fulda, Simone ;
Sipos, Bence ;
Johnstone, Ricky W. ;
Lauer, Ulrich M. ;
Bitzer, Michael .
MOLECULAR CANCER THERAPEUTICS, 2013, 12 (10) :2226-2236
[46]   Epigenetic action of decitabine (5-aza-2′-deoxycytidine) is more effective against acute myeloid leukemia than cytotoxic action of cytarabine (ARA-C) [J].
Momparler, Richard L. ;
Cote, Sylvie ;
Momparler, Louise F. .
LEUKEMIA RESEARCH, 2013, 37 (08) :980-984
[47]   Effect of 5-aza-2′-deoxycytidine and vitamin D3 analogs on growth and differentiation of human myeloid leukemic cells [J].
Benoit T. Doré ;
Christine Chomienne ;
Richard L. Momparler .
Cancer Chemotherapy and Pharmacology, 1998, 41 :275-280
[48]   Effect of 5-aza-2′-deoxycytidine and vitamin D3 analogs on growth and differentiation of human myeloid leukemic cells [J].
Doré, BT ;
Chomienne, C ;
Momparler, RL .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1998, 41 (04) :275-280
[49]   5-Aza-2′-deoxycytidine-mediated DNA hypomethylation with and without concurrent insulin resistance suppresses myotube mitochondrial capacity [J].
Rivera, Caroline N. ;
Kamer, Madison M. ;
Cook, Norah E. ;
McGovern, Macey R. ;
Watne, Rachel M. ;
Wommack, Andrew J. ;
Vaughan, Roger A. .
CELL BIOCHEMISTRY AND FUNCTION, 2023, 41 (08) :1422-1429
[50]   Phase I study of 5-aza-2′-deoxycytidine in combination with valproic acid in non-small-cell lung cancer [J].
Chu, B. F. ;
Karpenko, M. J. ;
Liu, Z. ;
Aimiuwu, J. ;
Villalona-Calero, M. A. ;
Chan, K. K. ;
Grever, M. R. ;
Otterson, G. A. .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2013, 71 (01) :115-121