Arsenic in the treatment of newly diagnosed acute promyelocytic leukemia: current status and future research direction
Jiong HU
Arsenic in the treatment of newly diagnosed acute promyelocytic leukemia: current status and future research direction
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia. In past decades, intensive studies on the biology and treatment of this disease have resulted in a remarkably thorough understanding of its pathogenesis and improvement of treatment outcomes. In particular, the introduction of all-trans retinoic acid to conventional chemotherapy improved dramatically the remission and survival rates of APL patients and consequently became the major treatment modality for it. In the last decade, the groundbreaking development of arsenic further improved the survival rate of APL patients. As the most active agent in APL, arsenic directly degrades the PML-RARα fusion transcript, leading to the differentiation and apoptosis of leukemia cells and the potential eradication of APL leukemia-initiating cells (LICs), thus making the disease a potentially curable type of leukemia. More notably, the recent development of oral arsenic compounds may further enhance not only clinical outcomes but also the convenience of patients, which may dramatically change the APL clinical scenario in the near future.
acute promyelocytic leukemia / arsenic / all-trans retinoic acid / survival
[1] |
Rowley J D, Golomb H M, Dougherty C. 15/17 translocation, a consistent chromosomal change in acute promyelocytic leukaemia. Lancet, 1977, 1(8010): 549–550
CrossRef
Pubmed
Google scholar
|
[2] |
Rousselot P, Hardas B, Patel A, Guidez F, Gäken J, Castaigne S, Dejean A, de Thé H, Degos L, Farzaneh F,
Pubmed
|
[3] |
Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood, 2008, 111(5):2505–2515
|
[4] |
Huang M E, Ye Y C, Chen S R, Chai J R, Lu J X, Zhoa L, Gu L J, Wang Z Y. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood, 1988, 72(2): 567–572
Pubmed
|
[5] |
Rodeghiero F, Avvisati G, Castaman G, Barbui T, Mandelli F. Early deaths and anti-hemorrhagic treatments in acute promyelocytic leukemia. A GIMEMA retrospective study in 268 consecutive patients. Blood, 1990, 75(11): 2112–2117
Pubmed
|
[6] |
Sanz M A, Martín G, Rayón C, Esteve J, González M, Díaz-Mediavilla J, Bolufer P, Barragán E, Terol M J, González J D, Colomer D, Chillón C, Rivas C, Gómez T, Ribera J M, Bornstein R, Román J, Calasanz M J, Arias J, Alvarez C, Ramos F, Debén G. A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia. PETHEMA group. Blood, 1999, 94(9): 3015–3021
Pubmed
|
[7] |
Kelaidi C, Chevret S, De Botton S, Raffoux E, Guerci A, Thomas X, Pigneux A, Lamy T, Rigal-Huguet F, Meyer-Monard S, Chevallier P, Maloisel F, Deconinck E, Ferrant A, Fegueux N, Ifrah N, Sanz M, Dombret H, Fenaux P, Adès L. Improved outcome of acute promyelocytic leukemia with high WBC counts over the last 15 years: the European APL Group experience. J Clin Oncol, 2009, 27(16): 2668–2676
CrossRef
Pubmed
Google scholar
|
[8] |
Tallman M S, Altman J K. How I treat acute promyelocytic leukemia. Blood, 2009, 114(25): 5126–5135
CrossRef
Pubmed
Google scholar
|
[9] |
Shen Z X, Chen G Q, Ni J H, Li X S, Xiong S M, Qiu Q Y, Zhu J, Tang W, Sun G L, Yang K Q, Chen Y, Zhou L, Fang Z W, Wang Y T, Ma J, Zhang P, Zhang T D, Chen S J, Chen Z, Wang Z Y. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood, 1997, 89(9): 3354–3360
Pubmed
|
[10] |
Chen G Q, Zhu J, Shi X G, Ni J H, Zhong H J, Si G Y, Jin X L, Tang W, Li X S, Xong S M, Shen Z X, Sun G L, Ma J, Zhang P, Zhang T D, Gazin C, Naoe T, Chen S J, Wang Z Y, Chen Z. In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood, 1996, 88(3): 1052–1061
Pubmed
|
[11] |
Niu C, Yan H, Yu T, Sun H P, Liu J X, Li X S, Wu W, Zhang F Q, Chen Y, Zhou L, Li J M, Zeng X Y, Yang R R, Yuan M M, Ren M Y, Gu F Y, Cao Q, Gu B W, Su X Y, Chen G Q, Xiong S M, Zhang T D, Waxman S, Wang Z Y, Chen Z, Hu J, Shen Z X, Chen S J. Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients. Blood, 1999, 94(10): 3315–3324
Pubmed
|
[12] |
Soignet S L, Frankel S R, Douer D, Tallman M S, Kantarjian H, Calleja E, Stone R M, Kalaycio M, Scheinberg D A, Steinherz P, Sievers E L, Coutré S, Dahlberg S, Ellison R, Warrell R P Jr. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol, 2001, 19(18): 3852–3860
Pubmed
|
[13] |
Mathews V, George B, Lakshmi K M, Viswabandya A, Bajel A, Balasubramanian P, Shaji R V, Srivastava V M, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood, 2006, 107(7): 2627–2632
CrossRef
Pubmed
Google scholar
|
[14] |
Mathews V, George B, Chendamarai E, Lakshmi K M, Desire S, Balasubramanian P, Viswabandya A, Thirugnanam R, Abraham A, Shaji R V, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J Clin Oncol, 2010, 28(24): 3866–3871
CrossRef
Pubmed
Google scholar
|
[15] |
Ghavamzadeh A, Alimoghaddam K, Ghaffari S H, Rostami S, Jahani M, Hosseini R, Mossavi A, Baybordi E, Khodabadeh A, Iravani M, Bahar B, Mortazavi Y, Totonchi M, Aghdami N. Treatment of acute promyelocytic leukemia with arsenic trioxide without ATRA and/or chemotherapy. Ann Oncol, 2006, 17(1): 131–134
CrossRef
Pubmed
Google scholar
|
[16] |
Zhang P, Wang S, Hu L, Qiu F, Yang H, Xiao Y, Li X, Han X, Zhou J, Liu P. Seven years' summary report on the treatment of acute promyelocytic leukemia with arsenic trioxide-an analysis of 242 cases. Chin J Hematol, 2000, 21(2): 67–70
|
[17] |
Zhou G B, Zhang J, Wang Z Y, Chen S J, Chen Z. Treatment of acute promyelocytic leukaemia with all-trans retinoic acid and arsenic trioxide: a paradigm of synergistic molecular targeting therapy. Philos Trans R Soc Lond B Biol Sci, 2007, 362(1482): 959–971
CrossRef
Pubmed
Google scholar
|
[18] |
Lallemand-Breitenbach V, Guillemin M C, Janin A, Daniel M T, Degos L, Kogan S C, Bishop J M, de Thé H. Retinoic acid and arsenic synergize to eradicate leukemic cells in a mouse model of acute promyelocytic leukemia. J Exp Med, 1999, 189(7): 1043–1052
CrossRef
Pubmed
Google scholar
|
[19] |
Jing Y, Wang L, Xia L, Chen G Q, Chen Z, Miller W H, Waxman S. Combined effect of all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia cells in vitro and in vivo. Blood, 2001, 97(1): 264–269
CrossRef
Pubmed
Google scholar
|
[20] |
Raffoux E, Rousselot P, Poupon J, Daniel M T, Cassinat B, Delarue R, Taksin A L, Réa D, Buzyn A, Tibi A, Lebbé G, Cimerman P, Chomienne C, Fermand J P, de Thé H, Degos L, Hermine O, Dombret H. Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia. J Clin Oncol, 2003, 21(12): 2326–2334
CrossRef
Pubmed
Google scholar
|
[21] |
Shen Z X, Shi Z Z, Fang J, Gu B W, Li J M, Zhu Y M, Shi J Y, Zheng P Z, Yan H, Liu Y F, Chen Y, Shen Y, Wu W, Tang W, Waxman S, De Thé H, Wang Z Y, Chen S J, Chen Z. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci USA, 2004, 101(15): 5328–5335
CrossRef
Pubmed
Google scholar
|
[22] |
Hu J, Liu Y F, Wu C F, Xu F, Shen Z X, Zhu Y M, Li J M, Tang W, Zhao W L, Wu W, Sun H P, Chen Q S, Chen B, Zhou G B, Zelent A, Waxman S, Wang Z Y, Chen S J, Chen Z. Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci USA, 2009, 106(9): 3342–3347
CrossRef
Pubmed
Google scholar
|
[23] |
Estey E, Garcia-Manero G, Ferrajoli A, Faderl S, Verstovsek S, Jones D, Kantarjian H. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood, 2006, 107(9): 3469–3473
CrossRef
Pubmed
Google scholar
|
[24] |
Ravandi F, Estey E, Jones D, Faderl S, O’Brien S, Fiorentino J, Pierce S, Blamble D, Estrov Z, Wierda W, Ferrajoli A, Verstovsek S, Garcia-Manero G, Cortes J, Kantarjian H. Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol, 2009, 27(4): 504–510
CrossRef
Pubmed
Google scholar
|
[25] |
Powell B L, Moser B, Stock W, Gallagher R E, Willman C L, Stone R M, Rowe J M, Coutre S, Feusner J H, Gregory J, Couban S, Appelbaum F R, Tallman M S, Larson R A. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood, 2010, 116(19): 3751–3757
CrossRef
Pubmed
Google scholar
|
[26] |
Sanz M A, Grimwade D, Tallman M S, Lowenberg B, Fenaux P, Estey E H, Naoe T, Lengfelder E, Büchner T, Döhner H, Burnett A K, Lo-Coco F. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood, 2009, 113(9): 1875–1891
CrossRef
Pubmed
Google scholar
|
[27] |
Zhu J, Lallemand-Breitenbach V, de Thé H. Pathways of retinoic acid- or arsenic trioxide-induced PML/RARalpha catabolism, role of oncogene degradation in disease remission. Oncogene, 2001, 20(49): 7257–7265
CrossRef
Pubmed
Google scholar
|
[28] |
Zhu J, Zhou J, Peres L, Riaucoux F, Honoré N, Kogan S, de Thé H. A sumoylation site in PML/RARA is essential for leukemic transformation. Cancer Cell, 2005, 7(2): 143–153
CrossRef
Pubmed
Google scholar
|
[29] |
Lallemand-Breitenbach V, Zhu J, Puvion F, Koken M, Honoré N, Doubeikovsky A, Duprez E, Pandolfi P P, Puvion E, Freemont P, de Thé H. Role of promyelocytic leukemia (PML) sumolation in nuclear body formation, 11S proteasome recruitment, and As2O3-induced PML or PML/retinoic acid receptor alpha degradation. J Exp Med, 2001, 193(12): 1361–1371
CrossRef
Pubmed
Google scholar
|
[30] |
Zhang X W, Yan X J, Zhou Z R, Yang F F, Wu Z Y, Sun H B, Liang W X, Song A X, Lallemand-Breitenbach V, Jeanne M, Zhang Q Y, Yang H Y, Huang Q H, Zhou G B, Tong J H, Zhang Y, Wu J H, Hu H Y, de Thé H, Chen S J, Chen Z. Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML. Science, 2010, 328(5975): 240–243
CrossRef
Pubmed
Google scholar
|
[31] |
Nasr R, Lallemand-Breitenbach V, Zhu J, Guillemin M C, de Thé H. Therapy-induced PML/RARA proteolysis and acute promyelocytic leukemia cure. Clin Cancer Res, 2009, 15(20): 6321–6326
CrossRef
Pubmed
Google scholar
|
[32] |
Wang J C, Dick J E. Cancer stem cells: lessons from leukemia. Trends Cell Biol, 2005, 15(9): 494–501
CrossRef
Pubmed
Google scholar
|
[33] |
Grignani F, Ferrucci P F, Testa U, Talamo G, Fagioli M, Alcalay M, Mencarelli A, Grignani F, Peschle C, Nicoletti I,
CrossRef
Pubmed
Google scholar
|
[34] |
Du C, Redner R L, Cooke M P, Lavau C. Overexpression of wild-type retinoic acid receptor alpha (RARalpha) recapitulates retinoic acid-sensitive transformation of primary myeloid progenitors by acute promyelocytic leukemia RARalpha-fusion genes. Blood, 1999, 94(2): 793–802
Pubmed
|
[35] |
Nasr R, Guillemin M C, Ferhi O, Soilihi H, Peres L, Berthier C, Rousselot P, Robledo-Sarmiento M, Lallemand-Breitenbach V, Gourmel B, Vitoux D, Pandolfi P P, Rochette-Egly C, Zhu J, de Thé H. Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation. Nat Med, 2008, 14(12): 1333–1342
CrossRef
Pubmed
Google scholar
|
[36] |
Delva L, Cornic M, Balitrand N, Guidez F, Micléa J M, Delmer A, Teillet F, Fenaux P, Castaigne S, Degos L,
Pubmed
|
[37] |
Zheng X, Seshire A, Rüster B, Bug G, Beissert T, Puccetti E, Hoelzer D, Henschler R, Ruthardt M. Arsenic but not all-trans retinoic acid overcomes the aberrant stem cell capacity of PML/RARalpha-positive leukemic stem cells. Haematologica, 2007, 92(3): 323–331
CrossRef
Pubmed
Google scholar
|
[38] |
Kogan S C. Curing APL: differentiation or destruction? Cancer Cell, 2009, 15(1): 7–8
CrossRef
Pubmed
Google scholar
|
[39] |
Ito K, Bernardi R, Morotti A, Matsuoka S, Saglio G, Ikeda Y, Rosenblatt J, Avigan D E, Teruya-Feldstein J, Pandolfi P P. PML targeting eradicates quiescent leukaemia-initiating cells. Nature, 2008, 453(7198): 1072–1078
CrossRef
Pubmed
Google scholar
|
[40] |
Luesink M, Pennings J L, Wissink W M, Linssen P C, Muus P, Pfundt R, de Witte T J, van der Reijden B A, Jansen J H. Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome. Blood, 2009, 114(27): 5512–5521
CrossRef
Pubmed
Google scholar
|
[41] |
Tallman M S, Andersen J W, Schiffer C A, Appelbaum F R, Feusner J H, Ogden A, Shepherd L, Rowe J M, François C, Larson R S, Wiernik P H. Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome. Blood, 2000, 95(1): 90–95
Pubmed
|
[42] |
Ng J C, Wang J, Shraim A. A global health problem caused by arsenic from natural sources. Chemosphere, 2003, 52(9): 1353–1359
CrossRef
Pubmed
Google scholar
|
[43] |
Ficker E, Kuryshev Y A, Dennis A T, Obejero-Paz C, Wang L, Hawryluk P, Wible B A, Brown A M. Mechanisms of arsenic-induced prolongation of cardiac repolarization. Mol Pharmacol, 2004, 66(1): 33–44
CrossRef
Pubmed
Google scholar
|
[44] |
Kojima C, Ramirez D C, Tokar E J, Himeno S, Drobná Z, Stýblo M, Mason R P, Waalkes M P. Requirement of arsenic biomethylation for oxidative DNA damage. J Natl Cancer Inst, 2009, 101(24): 1670–1681
CrossRef
Pubmed
Google scholar
|
[45] |
Hughes M F. Arsenic methylation, oxidative stress and cancer—is there a link? J Natl Cancer Inst, 2009, 101(24): 1660–1661
CrossRef
Pubmed
Google scholar
|
[46] |
Lu D P, Qiu J Y, Jiang B, Wang Q, Liu K Y, Liu Y R, Chen S S. Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia: a pilot report. Blood, 2002, 99(9): 3136–3143
CrossRef
Pubmed
Google scholar
|
[47] |
The Cooperation Group of Phase II Clinical Trial of Compound Huangdai Tablet. Phase II clinical trial of compound Huangdai tablet in newly diagnosed acute promyelocytic leukemia. Chin J Hematol, 2006, 27(12): 801–804
|
[48] |
Sun F, Chen N N, Cheng Y B. Compound realgar and natural indigo tablets in treatment of acute promyelocytic leukemia: a summary of experience in 204 cases. Zhong Xi Yi Jie He Xue Bao, 2008, 6(6): 639–642
CrossRef
Pubmed
Google scholar
|
[49] |
Au W Y, Kumana C R, Kou M, Mak R, Chan G C, Lam C W, Kwong Y L. Oral arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia. Blood, 2003, 102(1): 407–408
CrossRef
Pubmed
Google scholar
|
[50] |
Siu C W, Au W Y, Yung C, Kumana C R, Lau C P, Kwong Y L, Tse H F. Effects of oral arsenic trioxide therapy on QT intervals in patients with acute promyelocytic leukemia: implications for long-term cardiac safety. Blood, 2006, 108(1): 103–106
CrossRef
Pubmed
Google scholar
|
/
〈 | 〉 |