An overview of arsenic trioxide-involved combined treatment algorithms for leukemia: basic concepts and clinical implications

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Arsenic trioxide is a first-line treatment drug for acute promyelocytic leukemia, which is also effective for other kinds of leukemia. Its side effects, however, limit its clinical application, especially for patients with complex leukemia symptoms. Combination therapy can effectively alleviate these problems. This review summarizes the research progress on the combination of arsenic trioxide with anticancer drugs, vitamin and vitamin analogs, plant products, and other kinds of drugs in the treatment of leukemia. Additionally, the new progress in arsenic trioxide-induced cardiotoxicity was summarized. This review aims to provide new insights for the rational clinical application of arsenic trioxide.

Related collections

Most cited references 146

Record: found
Abstract: found
Article: found

Is Open Access

Targeting FLT3 mutations in AML: review of current knowledge and evidence

Naval Daver, Richard F Schlenk, Nigel Russell … (2019)

Genomic investigations of acute myeloid leukemia (AML) have demonstrated that several genes are recurrently mutated, leading to new genomic classifications, predictive biomarkers, and new therapeutic targets. Mutations of the FMS-like tyrosine kinase 3 (FLT3) gene occur in approximately 30% of all AML cases, with the internal tandem duplication (ITD) representing the most common type of FLT3 mutation (FLT3-ITD; approximately 25% of all AML cases). FLT3-ITD is a common driver mutation that presents with a high leukemic burden and confers a poor prognosis in patients with AML. The prognostic value of a FLT3 mutation in the tyrosine kinase domain (FLT3-TKD), which has a lower incidence in AML (approximately 7–10% of all cases), is uncertain. Accumulating evidence demonstrates that FLT3 mutational status evolves throughout the disease continuum. This so-called clonal evolution, together with the identification of FLT3-ITD as a negative prognostic marker, serves to highlight the importance of FLT3-ITD testing at diagnosis and again at relapse. Earlier identification of FLT3 mutations will help provide a better understanding of the patient’s disease and enable targeted treatment that may help patients achieve longer and more durable remissions. First-generation FLT3 inhibitors developed for clinical use are broad-spectrum, multikinase inhibitors; however, next-generation FLT3 inhibitors are more specific, more potent, and have fewer toxicities associated with off-target effects. Primary and secondary acquired resistance to FLT3 inhibitors remains a challenge and provides a rationale for combining FLT3 inhibitors with other therapies, both conventional and investigational. This review focuses on the pathological and prognostic role of FLT3 mutations in AML, clinical classification of the disease, recent progress with next-generation FLT3 inhibitors, and mechanisms of resistance to FLT3 inhibitors.

0 comments Cited 323 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

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

Z. -X. Shen, G Q Chen, J. H. Ni … (1997)

The therapeutic effect of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL) was evaluated among 15 APL patients at relapse after all-trans retinoic acid (ATRA) induced and chemotherapy maintained complete remission (CR). As2O3 was administered intravenously at the dose of 10 mg/d. Clinical CR was achieved in nine of 10 (90%) patients treated with As2O3 alone and in the remaining five patients treated by the combination of As2O3 and low-dose chemotherapeutic drugs or ATRA. During the treatment with As2O3, there was no bone marrow depression and only limited side effects were encountered. Pharmacokinetic studies, which were performed in eight patients, showed that after a peak level of 5.54 micromol/L to 7.30 micromol/L, plasma arsenic was rapidly eliminated, and the continuous administration of As2O3 did not alter its pharmacokinetic behaviors. In addition, increased amounts of arsenic appeared in the urine, with a daily excretion accounting for approximately 1% to 8% of the total daily dose administered. Arsenic contents in hair and nail were increased, and the peak content of arsenic could reach 2.5 to 2.7 microg/g tissue at CR. On the other hand, a decline of the arsenic content in hair and nail was observed after withdrawal of the drug. We conclude that As2O3 treatment is an effective and relatively safe drug in APL patients refractory to ATRA and conventional chemotherapy.

0 comments Cited 183 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide.

David Scheinberg, S L Soignet, S Jhanwar … (1998)

Two reports from China have suggested that arsenic trioxide can induce complete remissions in patients with acute promyelocytic leukemia (APL). We evaluated this drug in patients with APL in an attempt to elucidate its mechanism of action. Twelve patients with APL who had relapsed after extensive prior therapy were treated with arsenic trioxide at doses ranging from 0.06 to 0.2 mg per kilogram of body weight per day until visible leukemic cells were eliminated from the bone marrow. Bone marrow mononuclear cells were serially monitored by flow cytometry for immunophenotype, fluorescence in situ hybridization, reverse-transcription-polymerase-chain-reaction (RT-PCR) assay for PML-RAR-alpha fusion transcripts, and Western blot analysis for expression of the apoptosis-associated proteins caspases 1, 2, and 3. Of the 12 patients studied, 11 achieved complete remission after treatment that lasted from 12 to 39 days (range of cumulative doses, 160 to 495 mg). Adverse effects were relatively mild and included rash, lightheadedness, fatigue, and musculoskeletal pain. Cells that expressed both CD11b and CD33 (antigens characteristic of mature and immature cells, respectively), and which were found by fluorescence in situ hybridization to carry the t(15;17) translocation, increased progressively in number during treatment and persisted in the early phase of complete remission. Eight of 11 patients who initially tested positive for the PML-RAR-alpha fusion transcript by the RT-PCR assay later tested negative; 3 other patients, who persistently tested positive, relapsed early. Arsenic trioxide induced the expression of the proenzymes of caspase 2 and caspase 3 and activation of both caspase 1 and caspase 3. Low doses of arsenic trioxide can induce complete remissions in patients with APL who have relapsed. The clinical response is associated with incomplete cytodifferentiation and the induction of apoptosis with caspase activation in leukemic cells.

0 comments Cited 156 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Yanan Jiang:

ORCID: http://orcid.org/0000-0003-4202-3676

jiangyanan@hrbmu.edu.cn

Baofeng Yang:

ORCID: http://orcid.org/0000-0002-0125-1608

yangbf@ems.hrbmu.edu.cn

Yunlong Bai:

ORCID: http://orcid.org/0000-0002-5095-3382

baiyunlong@ems.hrbmu.edu.cn

Journal

Journal ID (nlm-ta): Cell Death Discov

Journal ID (iso-abbrev): Cell Death Discov

Title: Cell Death Discovery

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2058-7716

Publication date (Electronic): 27 July 2023

Publication date PMC-release: 27 July 2023

Publication date Collection: 2023

Volume: 9

Electronic Location Identifier: 266

Affiliations

[1 ]GRID grid.410736.7, ISNI 0000 0001 2204 9268, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, , Harbin Medical University, ; Harbin, China

[2 ]GRID grid.410736.7, ISNI 0000 0001 2204 9268, Translational Medicine Research and Cooperation Center of Northern China, , Heilongjiang Academy of Medical Sciences, ; Harbin, China

[3 ]GRID grid.412651.5, ISNI 0000 0004 1808 3502, Department of Gastrointestinal Medical Oncology, , Harbin Medical University Cancer Hospital, ; Harbin, China

[4 ]GRID grid.410736.7, ISNI 0000 0001 2204 9268, College of Bioinformatics Science and Technology, , Harbin Medical University, ; Harbin, China

[5 ]Research Unit of Noninfectious Chronic Diseases in Frigid Zone, Chinese Academy of Medical Sciences (2019RU070), Harbin, China

Author information

Yanan Jiang http://orcid.org/0000-0003-4202-3676

Juan Xu http://orcid.org/0000-0002-3709-4165

Baofeng Yang http://orcid.org/0000-0002-0125-1608

Yunlong Bai http://orcid.org/0000-0002-5095-3382

Article

Publisher ID: 1558

DOI: 10.1038/s41420-023-01558-z

PMC ID: 10374529

PubMed ID: 37500645

SO-VID: 2c753a2b-1305-4f8c-adc7-7b20153191af

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 7 February 2023

Date revision received : 20 June 2023

Date accepted : 14 July 2023

Funding

Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);

Award ID: 81803524

Award ID: 82170240

Award Recipient : Yanan Jiang Yunlong Bai

Funded by: FundRef https://doi.org/10.13039/501100005046, Natural Science Foundation of Heilongjiang Province;

Award ID: LH2021H018

Award Recipient : Yanan Jiang

Funded by: the Heilongjiang Postdoctoral Foundation (Grant No. LBH-Q21134).

Custom metadata

Keywords: cancer therapy,drug development

Data availability:

Keywords: cancer therapy, drug development

Comments

Comment on this article

scite_

Smart Citations

Citing PublicationsSupportingMentioningContrasting

View Citations

See how this article has been cited at scite.ai

scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

Cited by 11

See all cited by

Most referenced authors 2,027

See all reference authors

An overview of arsenic trioxide-involved combined treatment algorithms for leukemia: basic concepts and clinical implications

Read this article at

Abstract

Related collections

cGMP: Generators, Effectors and Therapeutic Implications Conference

Most cited references 146

Targeting FLT3 mutations in AML: review of current knowledge and evidence

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

Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide.

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 898

Cited by 11

Most referenced authors 2,027