When Poisons Cure: The Case of Arsenic in Acute Promyelocytic Leukemia

2.

Rowley

JD

,

Golomb

HM

,

Dougherty

C

.

15/17 translocation, a consistent chromosomal change in acute promyelocytic leukaemia

.

Lancet

.

1977 Mar 5

;

1

(

8010

):

549

–

50

.

3.

Pandolfi

PP

,

Alcalay

M

,

Fagioli

M

,

Zangrilli

D

,

Mencarelli

A

,

Diverio

D

, .

Genomic variability and alternative splicing generate multiple PML/RAR alpha transcripts that encode aberrant PML proteins and PML/RAR alpha isoforms in acute promyelocytic leukaemia

.

Embo J

.

1992 Apr

;

11

(

4

):

1397

–

407

.

4.

Sanz

MA

,

Grimwade

D

,

Tallman

MS

,

Lowenberg

B

,

Fenaux

P

,

Estey

EH

, .

Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet

.

Blood

.

2019 Apr 11

;

113

(

9

):

1875

–

91

.

5.

de

Thé

H

,

Chomienne

C

,

Lanotte

M

,

Degos

L

,

Dejean

A

.

The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus

.

Nature

.

1990 Oct 11

;

347

(

6293

):

558

–

61

.

6.

Borrow

J

,

Goddard

AD

,

Gibbons

B

,

Katz

F

,

Swirsky

D

,

Fioretos

T

, .

Diagnosis of acute promyelocytic leukaemia by RT-PCR: detection of PML-RARA and RARA-PML fusion transcripts

.

Br J Haematol

.

1992 Nov

;

82

(

3

):

529

–

40

.

7.

Borrow

J

,

Solomon

E

.

Molecular analysis of the t(15;17) translocation in acute promyelocytic leukaemia

.

Baillieres Clin Haematol

.

1992 Oct

;

5

(

4

):

833

–

56

.

8.

Arber

DA

,

Orazi

A

,

Hasserjian

R

,

Thiele

J

,

Borowitz

MJ

,

Le Beau

MM

, .

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

.

Blood

.

2016 May 19

;

127

(

20

):

2391

–

405

.

9.

Guo

A

,

Salomoni

P

,

Luo

J

,

Shih

A

,

Zhong

S

,

Gu

W

, .

The function of PML in p53-dependent apoptosis

.

Nat Cell Biol

.

2000 Oct

;

2

(

10

):

730

–

6

.

10.

de Thé

H

.

Differentiation therapy revisited

.

Nat Rev Cancer

.

2018 Feb

;

18

(

2

):

117

–

27

.

11.

Dos Santos

GA

,

Kats

L

,

Pandolfi

PP

.

Synergy against PML-RARa: targeting transcription, proteolysis, differentiation, and self-renewal in acute promyelocytic leukemia

.

J Exp Med

.

2013 Dec 16

;

210

(

13

):

2793

–

802

.

12.

Lo-Coco

F

,

Hasan

SK

.

Understanding the molecular pathogenesis of acute promyelocytic leukemia

.

Best Pract Res Clin Haematol

.

2014 Mar

;

27

(

1

):

3

–

9

.

13.

Kwok

C

,

Zeisig

BB

,

Dong

S

,

So

CW

.

Forced homo-oligomerization of RARalpha leads to transformation of primary hematopoietic cells

.

Cancer Cell

.

2006 Feb

;

9

(

2

):

95

–

108

.

14.

Nasr

R

,

Guillemin

MC

,

Ferhi

O

,

Soilihi

H

,

Peres

L

,

Berthier

C

, .

Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation

.

Nat Med

.

2008 Dec

;

14

(

12

):

1333

–

42

.

15.

Lallemand-Breitenbach

V

,

Jeanne

M

,

Benhenda

S

,

Nasr

R

,

Lei

M

,

Peres

L

, .

Arsenic degrades PML or PML-RARalpha through a SUMO-triggered RNF4/ubiquitin-mediated pathway

.

Nat Cell Biol

.

2008 May

;

10

(

5

):

547

–

55

.

16.

Ablain

J

,

Rice

K

,

Soilihi

H

,

de

Reynies

A

,

Minucci

S

,

de

Thé

H

.

Activation of a promyelocytic leukemia-tumor protein 53 axis underlies acute promyelocytic leukemia cure

.

Nat Med

.

2014 Feb

;

20

(

2

):

167

–

74

.

17.

Rao

Y

,

Li

R

,

Zhang

D

.

A drug from poison: how the therapeutic effect of arsenic trioxide on acute promyelocytic leukemia was discovered

.

Sci China Life Sci

.

2013 Jun

;

56

(

6

):

495

–

502

.

18.

Hughes

MF

,

Beck

BD

,

Chen

Y

,

Lewis

AS

,

Thomas

DJ

.

Arsenic exposure and toxicology: a historical perspective

.

Toxicol Sci

.

2011 Oct

;

123

(

2

):

305

–

32

.

19.

Jolliffe

DM

.

A history of the use of arsenicals in man

.

J R Soc Med

.

1993 May

;

86

(

5

):

287

–

9

.

20.

Antman

KH

.

Introduction: the history of arsenic trioxide in cancer therapy

.

Oncologist

.

2001

;

6

(

Suppl 2

):

1

–

2

.

21.

Koeffler

HP

.

Induction of differentiation of human acute myelogenous leukemia cells: therapeutic implications

.

Blood

.

1983 Oct

;

62

(

4

):

709

–

21

.

22.

Warrell

RP

Jr,

Frankel

SR

,

Miller

WH

Jr,

Scheinberg

DA

,

Itri

LM

,

Hittelman

WN

, .

Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid)

.

N Engl J Med

.

1991 May 16

;

324

(

20

):

1385

–

93

.

23.

Huang

M

,

Ye

Y

,

Chen

S

,

Chai

J

,

Lu

J

,

Zhoa

L

, .

Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia

.

Blood

.

1988

;

72

(

2

):

567

–

72

.

Blood. 2016 Dec 29;128(26):3017

.http://dx.doi.org/10.1182/blood.v72.2.567.567[Check Journal Title]

24.

Chen

GQ

,

Zhu

J

,

Shi

XG

,

Ni

JH

,

Zhong

HJ

,

Si

GY

, .

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 Aug 1

;

88

(

3

):

1052

–

61

.

25.

Chen

GQ

,

Shi

XG

,

Tang

W

,

Xiong

SM

,

Zhu

J

,

Cai

X

, .

Use of arsenic trioxide (As₂O₃) in the treatment of acute promyelocytic leukemia (APL): I. As₂O₃ exerts dose-dependent dual effects on APL cells

.

Blood

.

1997 May 1

;

89

(

9

):

3345

–

53

.

26.

Lallemand-Breitenbach

V

,

Guillemin

MC

,

Janin

A

,

Daniel

MT

,

Degos

L

,

Kogan

SC

, .

Retinoic acid and arsenic synergize to eradicate leukemic cells in a mouse model of acute promyelocytic leukemia

.

J Exp Med

.

1999 Apr 5

;

189

(

7

):

1043

–

52

.

27.

Rego

EM

,

He

LZ

,

Warrell

RP

Jr,

Wang

ZG

,

Pandolfi

PP

.

Retinoic acid (RA) and As₂O₃ treatment in transgenic models of acute promyelocytic leukemia (APL) unravel the distinct nature of the leukemogenic process induced by the PML-RARalpha and PLZF-RARalpha oncoproteins

.

Proc Natl Acad Sci U S A

.

2000 Aug 29

;

97

(

18

):

10173

–

8

.

28.

Sanz

MA

,

Grimwade

D

,

Tallman

MS

,

Lowenberg

B

,

Fenaux

P

,

Estey

EH

, .

Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet

.

Blood

.

2009 Feb 26

;

113

(

9

):

1875

–

91

.

29.

Cortes

JE

,

Kantarjian

H

,

O’Brien

S

,

Robertson

LE

,

Koller

C

,

Hirsh-Ginsberg

C

, .

All-trans retinoic acid followed by chemotherapy for salvage of refractory or relapsed acute promyelocytic leukemia

.

Cancer

.

1994 Jun 15

;

73

(

12

):

2946

–

52

.

30.

Shen

ZX

,

Chen

GQ

,

Ni

JH

,

Li

XS

,

Xiong

SM

,

Qiu

QY

, .

Use of arsenic trioxide (As₂O₃) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients

.

Blood

.

1997 May 1

;

89

(

9

):

3354

–

60

.

31.

Soignet

SL

,

Frankel

SR

,

Douer

D

,

Tallman

MS

,

Kantarjian

H

,

Calleja

E

, .

United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia

.

J Clin Oncol

.

2001 Sep 15

;

19

(

18

):

3852

–

60

.

32.

Shen

ZX

,

Shi

ZZ

,

Fang

J

,

Gu

BW

,

Li

JM

,

Zhu

YM

, .

All-trans retinoic acid/As₂O₃ combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia

.

Proc Natl Acad Sci U S A

.

2004 Apr 13

;

101

(

15

):

5328

–

35

.

33.

Estey

E

,

Garcia-Manero

G

,

Ferrajoli

A

,

Faderl

S

,

Verstovsek

S

,

Jones

D

, .

Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia

.

Blood

.

2006 May 1

;

107

(

9

):

3469

–

73

.

34.

Sanz

MA

,

Lo

Coco

F

,

Martín

G

,

Avvisati

G

,

Rayón

C

,

Barbui

T

, .

Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups

.

Blood

.

2000 Aug 15

;

96

(

4

):

1247

–

53

.

.http://dx.doi.org/10.1182/blood-2012-02-410746

35.

Iland

HJ

,

Bradstock

K

,

Supple

SG

,

Catalano

A

,

Collins

M

,

Hertzberg

M

, .

All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4)

.

Blood

.

2012 Aug 23

;

120

(

8

):

1570

–

752

; quiz 752

36.

Powell

BL

,

Moser

B

,

Stock

W

,

Gallagher

RE

,

Willman

CL

,

Stone

RM

, .

Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710

.

Blood

.

2010 Nov 11

;

116

(

19

):

3751

–

7

.

37.

Mathews

V

,

Thomas

M

,

Srivastava

VM

,

George

B

,

Srivastava

A

,

Chandy

M

.

Impact of FLT3 mutations and secondary cytogenetic changes on the outcome of patients with newly diagnosed acute promyelocytic leukemia treated with a single agent arsenic trioxide regimen

.

Haematologica

.

2007 Jul

;

92

(

7

):

994

–

5

.

38.

Lo-Coco

F

,

Avvisati

G

,

Vignetti

M

,

Thiede

C

,

Orlando

SM

,

Iacobelli

S

, .

Retinoic acid and arsenic trioxide for acute promyelocytic leukemia

.

N Engl J Med

.

2013 Jul 11

;

369

(

2

):

111

–

21

.

39.

Montesinos

P

,

Bergua

JM

,

Vellenga

E

,

Rayón

C

,

Parody

R

,

de la Serna

J

, .

Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors

.

Blood

.

2009 Jan 22

;

113

(

4

):

775

–

83

.

40.

Cicconi

L

,

Platzbecker

U

,

Avvisati

G

,

Paoloni

F

,

Thiede

C

,

Vignetti

M

, .

Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial

.

Leukemia

.

2020 Mar

;

34

(

3

):

914

–

8

.

41.

Abaza

Y

,

Kantarjian

H

,

Garcia-Manero

G

,

Estey

E

,

Borthakur

G

,

Jabbour

E

, .

Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab

.

Blood

.

2017 Mar 9

;

129

(

10

):

1275

–

83

.

42.

Cicconi

L

,

Divona

M

,

Ciardi

C

,

Ottone

T

,

Ferrantini

A

,

Lavorgna

S

, .

PML-RARα kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukaemia treated with ATRA and ATO or ATRA and chemotherapy

.

Leukemia

.

2016 Oct

;

30

(

10

):

1987

–

92

.

43.

Burnett

AK

,

Russell

NH

,

Hills

RK

,

Bowen

D

,

Kell

J

,

Knapper

S

, .

Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial

.

Lancet Oncol

.

2015 Oct

;

16

(

13

):

1295

–

305

.

44.

Adès

L

,

Thomas

X

,

Bresler

AG

,

Raffoux

E

,

Spertini

O

,

Vey

N

, .

Arsenic trioxide is required in the treatment of newly diagnosed acute promyelocytic leukemia. Analysis of a randomized trial (APL 2006) by the French Belgian Swiss APL group

.

Haematologica

.

2018 Dec

;

103

(

12

):

2033

–

9

.

45.

Zhang

X

,

Zhang

H

,

Chen

L

,

Wang

M

,

Xi

J

,

Liu

X

, .

Arsenic trioxide and all-trans retinoic acid (ATRA) treatment for acute promyelocytic leukemia in all risk groups: study protocol for a randomized controlled trial

.

Trials

.

2018 Sep 5

;

19

(

1

):

476

.

46.

Efficace

F

,

Mandelli

F

,

Avvisati

G

,

Cottone

F

,

Ferrara

F

,

Di

Bona

E

, .

Randomized phase III trial of retinoic acid and arsenic trioxide versus retinoic acid and chemotherapy in patients with acute promyelocytic leukemia: health-related quality-of-life outcomes

.

J Clin Oncol

.

2014 Oct 20

;

32

(

30

):

3406

–

12

.

47.

Efficace

F

,

Breccia

M

,

Avvisati

G

,

Cottone

F

,

Intermesoli

T

,

Borlenghi

E

, .

Health-related quality of life, symptom burden, and comorbidity in long-term survivors of acute promyelocytic leukemia

.

Leukemia

.

2019 Jul

;

33

(

7

):

1598

–

607

.

48.

Kutny

MA

,

Alonzo

TA

,

Gerbing

RB

,

Wang

YC

,

Raimondi

SC

,

Hirsch

BA

, .

Arsenic trioxide consolidation allows anthracycline dose reduction for pediatric patients with acute promyelocytic leukemia: report from the children’s oncology group phase III historically controlled trial AAML0631

.

J Clin Oncol

.

2017 Sep 10

;

35

(

26

):

3021

–

9

.

.http://dx.doi.org/10.1002/pbc.26461

49.

Creutzig

U

,

Dworzak

MN

,

Bochennek

K

,

Faber

J

,

Flotho

C

,

Graf

N

, .

First experience of the AML-Berlin-Frankfurt-Münster group in pediatric patients with standard-risk acute promyelocytic leukemia treated with arsenic trioxide and all-trans retinoid acid

.

Pediatr Blood Cancer

.

2017 Aug

;

64

(

8

):

e26461

50.

Au

WY

,

Chim

CS

,

Lie

AK

,

Liang

R

,

Kwong

YL

,

Zecca

M

, .

Combined arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia recurring from previous relapses successfully treated using arsenic trioxide

.

Br J Haematol

.

2019 Apr

;

117

(

1

):

130

–

2

.

51.

Coombs

CC

,

DeAngelis

LM

,

Feusner

JH

,

Rowe

JM

,

Tallman

MS

.

Pseudotumor cerebri in acute promyelocytic leukemia patients on intergroup protocol 0129: clinical description and recommendations for new diagnostic criteria

.

Clin Lymphoma Myeloma Leuk

.

2016 Mar

;

16

(

3

):

146

–

51

.

.http://dx.doi.org/10.1038/s41375-020-0758-4

52.

Kayser

S

,

Rahmé

R

,

Martínez-Cuadrón

D

,

Ghiaur

G

,

Thomas

X

,

Sobas

M

, .

Outcome of older (≥70 years) APL patients frontline treated with or without arsenic trioxide: an International Collaborative Study

.

Leukemia

.

2020 Feb 19

53.

Lehmann

S

,

Deneberg

S

,

Antunovic

P

,

Rangert-Derolf

Å

,

Garelius

H

,

Lazarevic

V

, .

Early death rates remain high in high-risk APL: update from the Swedish Acute Leukemia Registry 1997–2013

.

Leukemia

.

2017 Jun

;

31

(

6

):

1457

–

9

.

54.

Rosati

S

,

Breccia

M

,

Gurnari

C

,

Carmosino

I

,

Scalzulli

E

,

Montefusco

E

, .

Acute promyelocytic leukemia (APL) in very elderly patients: real-life behind protocols

.

Blood

.

2019

;

134

(

Suppl 1

):

3845

.http://dx.doi.org/10.1182/blood-2019-129216[Check Journal Title]

55.

Zhu

HH

,

Hu

J

,

Lo-Coco

F

,

Jin

J

.

The simpler, the better: oral arsenic for acute promyelocytic leukemia

.

Blood

.

2019 Aug 15

;

134

(

7

):

597

–

605

.

56.

Qian

LZY

.

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

–

4

.

57.

Wang

L

,

Zhou

G

,

Liu

P

,

Song

J

,

Liang

Y

,

Yan

X

, .

Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia

.

Proc Natl Acad Sci U S A

.

2008 Mar 25

;

105

(

12

):

4826

–

31

.

58.

Zhu

HH

,

Wu

DP

,

Du

X

,

Zhang

X

,

Liu

L

,

Ma

J

, .

Oral arsenic plus retinoic acid versus intravenous arsenic plus retinoic acid for non-high-risk acute promyelocytic leukaemia: a non-inferiority, randomised phase 3 trial

.

Lancet Oncol

.

2018 Jul

;

19

(

7

):

871

–

9

.

59.

Zhu

HH

,

Huang

XJ

.

Oral arsenic and retinoic acid for non-high-risk acute promyelocytic leukemia

.

N Engl J Med

.

2014 Dec 4

;

371

(

23

):

2239

–

41

.

60.

Zhu

HH

,

Liu

YR

,

Jia

JS

,

Qin

YZ

,

Zhao

XS

,

Lai

YY

.

Oral arsenic and all-trans retinoic acid for high-risk acute promyelocytic leukemia

.

Blood

.

2018 Jun 28

;

131

(

26

):

2987

–

9

.

61.

Jiang

H

,

Liang

GW

,

Huang

XJ

,

Jiang

Q

,

Han

S

,

Shi

LW

, .

Reduced medical costs and hospital days when using oral arsenic plus ATRA as the first-line treatment of acute promyelocytic leukemia

.

Leuk Res

.

2015 Dec

;

39

(

12

):

1319

–

24

.

62.

Chen

Z

,

Guidez

F

,

Rousselot

P

,

Agadir

A

,

Chen

SJ

,

Wang

ZY

, .

PLZF-RAR alpha fusion proteins generated from the variant t(11;17)(q23;q21) translocation in acute promyelocytic leukemia inhibit ligand-dependent transactivation of wild-type retinoic acid receptors

.

Proc Natl Acad Sci U S A

.

1994 Feb 1

;

91

(

3

):

1178

–

82

.

63.

Ciangola

G

,

Gurnari

C

,

Paterno

G

,

Mirabile

M

,

Angelini

M

,

Lavorgna

S

, .

STAT5b-RARa-positive acute myeloid leukemia: diagnostic and therapeutic challenges of a rare AML subtype

.

Leuk Res

.

2019 Mar

;

78

:

21

–

3

.

64.

Noguera

NI

,

Catalano

G

,

Banella

C

,

Divona

M

,

Faraoni

I

,

Ottone

T

, .

Acute promyelocytic leukemia: update on the mechanisms of leukemogenesis, resistance and on innovative treatment strategies

.

Cancers

.

2019 Oct 18

;

11

(

10

):

1591

.

65.

Goto

E

,

Tomita

A

,

Hayakawa

F

,

Atsumi

A

,

Kiyoi

H

,

Naoe

T

.

Missense mutations in PML-RARA are critical for the lack of responsiveness to arsenic trioxide treatment

.

Blood

.

2011 Aug 11

;

118

(

6

):

1600

–

9

.

66.

Zhu

HH

,

Qin

YZ

,

Huang

XJ

.

Resistance to arsenic therapy in acute promyelocytic leukemia

.

N Engl J Med

.

2014 May 8

;

370

(

19

):

1864

–

6

.

67.

Lehmann-Che

J

,

Bally

C

,

de Thé

H

.

Resistance to therapy in acute promyelocytic leukemia

.

N Engl J Med

.

2014 Sep 18

;

371

(

12

):

1170

–

2

.

68.

Tomita

A

,

Kiyoi

H

,

Naoe

T

.

Mechanisms of action and resistance to all-trans retinoic acid (ATRA) and arsenic trioxide (As₂O₃) in acute promyelocytic leukemia

.

Int J Hematol

.

2013 Jun

;

97

(

6

):

717

–

25

.

69.

Iaccarino

L

,

Ottone

T

,

Divona

M

,

Cicconi

L

,

Cairoli

R

,

Voso

MT

, .

Mutations affecting both the rearranged and the unrearranged PML alleles in refractory acute promyelocytic leukaemia

.

Br J Haematol

.

2016 Mar

;

172

(

6

):

909

–

13

.

70.

Iaccarino

L

,

Ottone

T

,

Alfonso

V

,

Cicconi

L

,

Divona

M

,

Lavorgna

S

, .

Mutational landscape of patients with acute promyelocytic leukemia at diagnosis and relapse

.

Am J Hematol

.

2019 Oct

;

94

(

10

):

1091

–

7

.

71.

Madan

V

,

Shyamsunder

P

,

Han

L

,

Mayakonda

A

,

Nagata

Y

,

Sundaresan

J

, .

Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia

.

Leukemia

.

2016 Aug

;

30

(

12

):

2430

–

81

.