Maintenance therapy with all-trans retinoic acid and arsenic trioxide improves relapse-free survival in adults with low- to intermediate-risk acute promyelocytic leukemia who have achieved complete remission after consolidation therapy

Liang, Bin; Zheng, Zhouyi; Shi, Yifen; Chen, Jingjing; Hu, Xudong; Hu, Qian; Shen, Zhijian; Jiang, Songfu; Kang, Yu; Feng, Jianhua

doi:10.2147/ott.s135013

Cited by 12 publications

(9 citation statements)

References 39 publications

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“…Considering this, it was not surprising that subsequent studies found that APL patients cured by ATRA treatment relapsed at a median of 3.5 months after achieving remission 27 , 28 . Numerous studies demonstrated the combined ATRA with arsenic regimens drastically reduced relapse in adult patients with APL compared to ATRA treatments without arsenic 29 – 31 . We demonstrated that p11 and p36 protein levels are stimulated by the expression of the PML/RARα oncoprotein, and ATRA treatment of the APL cell line, NB4, results in the loss of p11 and p36 protein levels 9 .…”

Section: Introductionmentioning

confidence: 99%

Regulation of cell surface protease receptor S100A10 by retinoic acid therapy in acute promyelocytic leukemia (APL)☆

et al. 2018

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S100A10 (p11), a member of the S100 family of small dimeric EF-hand-type Ca2+-binding proteins, plays a role in a variety of both intracellular and extracellular processes. Previous studies have suggested that p11 is intrinsically unstable and requires binding to annexin A2 (p36) to prevent its rapid ubiquitylation and degradation. Our laboratory has shown that p11 levels are stimulated by the expression of the oncoprotein, PML/RARα. Furthermore, treatment of the APL cell line, NB4 with all-trans retinoic acid (ATRA) causes the rapid loss of p36 and p11 protein. However, the mechanism by which ATRA regulates p11 levels has not been established. Here, we show that the proteasomal inhibitor, lactacystin reversed the ATRA-dependent loss of p11, but did not cause an accumulation of ubiquitylated forms of p11, suggesting that ATRA promotes the proteasomal degradation of p11 in an ubiquitin-independent manner. ATRA treatment of MCF-7 breast cancer cells reduced p11 but not p36 transcript and protein levels, thus indicating that ATRA can regulate p11 levels independently of PML/RARα and p36. Overexpression of p36 upregulated p11 protein but not mRNA levels, indicating that p36 affects p11 post translationally. The forced expression of ubiquitin and p11 in 293 T cells resulted in ubiquitylation of p11 that was blocked by mutagenesis of lysine 57. This study highlights the complex regulation of p11 by retinoid signaling and challenges the hypothesis that ubiquitin-mediated proteasomal degradation of p11 represents a universal mechanism of regulation of this protein.

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Section: Introductionmentioning

confidence: 99%

Regulation of cell surface protease receptor S100A10 by retinoic acid therapy in acute promyelocytic leukemia (APL)☆

et al. 2018

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“…Patients with newly diagnosed APL, also known as a AML M3 subtype with APL-specific chromosomal translocation t(15;17) (q22;q21) and PML/RARα chimeric fusion protein, are mostly cured after standard ATRA with chemotherapy, while toxicity and refractoriness to the treatment are observed in some patients. Accumulating evidence shows the superiority of novel combined ATRA and ATO therapy for the treatment of patients with APL in terms of event-free survival, relapse-free survival, and less hematologic toxicity, compared to ATRA with chemotherapy [4,5,[69][70][71][72]. The molecular basis underlying synergistic effects between ATRA and ATO has been biologically demonstrated.…”

Section: Acute Promyelocytic Leukemia (Apl)mentioning

confidence: 99%

Arsenic-Based Anticancer-Combined Therapy: Novel Mechanism Inducing Apoptosis of Cancer Cells

Ota¹,

Wahiduzzaman²,

Hosokawa³

2018

Current Understanding of Apoptosis - Programmed Cell Death

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Arsenic, known as both a naturally occurring toxic element and a traditionally used drug, has caught a great deal of attention from worldwide people due to its curable anticancer effect in patients with acute promyelocytic leukemia (APL). Among the arsenicals, arsenic trioxide (ATO) has been the most widely used anticancer drug. Since ATO exerts an anticancer effect by mediating apoptosis, numerous studies have made efforts to uncover the molecular mechanisms by which ATO activates and/or mediates the apoptotic signaling pathway in cancer cells. Recent advances in cancer therapeutics have led to a paradigm shift away from the traditional cytotoxic drugs toward the targeting of proteins closely associated with driving the cancer phenotype. Here, we discuss novel current arsenic-based combination therapies to treat cancer in both clinical and experimental settings. We also discuss the novel molecular mechanism underlying apoptosis induced by the combined therapies.

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“…It has contributed to long term durable remissions and cures in other hematological diseases, such as acute lymphoblastic leukemia and follicular lymphoma, but its role in AML is still controversial. With the exception of arsenic trioxide and retinoic acid in acute promyelocytic leukemia, no maintenance therapy has demonstrated sufficient efficacy to be considered standard in the treatment of AML. The concept of maintenance therapy in AML is based on the premise that the induction therapies currently used are not able to ensure the complete elimination of the leukemic clone.…”

Section: Introductionmentioning

confidence: 99%

Maintenance therapy in AML: The past, the present and the future

et al. 2019

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Curative treatment in acute myeloid leukemia (AML) depends on successful induction therapy to achieve a complete remission (CR), and subsequent post‐remission therapy to prevent relapse. High relapse rates after consolidation therapy and after allogeneic stem cell transplant contribute to suboptimal outcomes in AML patients, and continue to represent a difficult challenge. Effective maintenance therapy could play an important role in prolonging the remission interval in the post‐consolidation setting, especially in high risk AML patients. Maintenance treatment approaches based on conventional chemotherapy, immunotherapy, hypomethylating agents, and targeted small molecules have been explored in this setting, but no data so far have been convincing enough to establish this approach as the standard of care. However, ongoing and future studies including novel targeted therapies may demonstrate promising efficacy that could facilitate incorporation of maintenance therapy into clinical practice. In this review we summarize previous and ongoing approaches of maintenance therapy in AML and discuss the most promising strategies.

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Maintenance therapy with all-trans retinoic acid and arsenic trioxide improves relapse-free survival in adults with low- to intermediate-risk acute promyelocytic leukemia who have achieved complete remission after consolidation therapy

Cited by 12 publications

References 39 publications

Regulation of cell surface protease receptor S100A10 by retinoic acid therapy in acute promyelocytic leukemia (APL)☆

Regulation of cell surface protease receptor S100A10 by retinoic acid therapy in acute promyelocytic leukemia (APL)☆

Arsenic-Based Anticancer-Combined Therapy: Novel Mechanism Inducing Apoptosis of Cancer Cells

Maintenance therapy in AML: The past, the present and the future

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