Clinical efficacy of all-trans retinoic acid for treating adult T cell leukemia

Maeda, Yasuhiro; Yamaguchi, Tadatoshi; Hijikata, Yasuki; Tanaka, Masuji; Hirase, Chikara; Takaı̈, Shinji; Morita, Yasuyoshi; Sano, Tetsuaki; Miyatake, Jun-ichi; Tatsumi, Yoichi; Kanamaru, Akihisa

doi:10.1007/s00432-007-0334-6

Cited by 26 publications

(17 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…94 Treatment results for 20 patients with ATL were recently reported. 95 The efficacy of ATRA was as follows : 2 PR, 2 no change (NC), 3 progressive disease (PD) in 7 acute type ATL, 3 PR in 3 lymphoma type ATL, 1 PR, 3 NC in 4 chronic type ATL, and 2 PR, 4 NC in 6 smoldering type ATL. These data suggest that retinoids are effective, but have limited efficacy.…”

Section: ) Retinoid Derivativesmentioning

confidence: 99%

Treatment of Adult T-cell Leukemia

Uozumi

2010

J Clin Exp Hematopathol

View full text Add to dashboard Cite

Adult T-cell Leukemia (ATL) is an aggressive malignant disease of CD4 + T-cells associated with human T-cell leukemia virus type I (HTLV-I). Prognosis of ATL patients is directly correlated to the subtype of ATL. Treatment of the aggressive forms (acute and lymphoma types) of ATL remains inadequate, as most ATL patients receive conventional chemotherapy without stem cell rescue. At present, LSG15 is the standard chemotherapy for the treatment of aggressive ATL, but the efficacy of LSG15 in most patients is transient. To prolong median survival time, additional therapies for maintenance of complete response (CR) are needed after achieving CR by induction chemotherapy. Improved outcome after allogeneic stem cell transplantation (allo-SCT), despite a high incidence of graft-versus-host disease, has been reported. Thus, allogeneic bone marrow transplantation and allogeneic peripheral blood SCT may have great potential for eradication of HTLV-1 and cure of ATL. Recently, reduced-intensity conditioning stem cell transplantation was also reported to be effective for ATL. Although several issues, including selection criteria for patients and sources of stem cells remain to be resolved, allo-SCT may be considered as a treatment option for patients with aggressive ATL. To evaluate whether allo-SCT is more effective than the standard chemotherapy (LSG15) for aggressive ATL, an upfront phase II clinical trial of JCOG-LSG is now being planned. Novel innovative targeted strategies, such as antiretroviral therapy, arsenic trioxide, nuclear factor-kB inhibitors, proteasome inhibitors, histone deacetylase inhibitors, several monoclonal antibodies including anti-CC chemokine receptor 4, anti-folate, purine nucleotide phosphorylase inhibitor, mTOR (mammalian target of rapamycin) inhibitor, bendamustine, small molecule Bcl-2 inhibitors and Tax-targeted immunotherapy, should be promptly studied in order to develop curative treatments for ATL in the near future. 〔J Clin Exp Hematopathol 50(1) : 9-25, 2010〕

show abstract

Section: ) Retinoid Derivativesmentioning

confidence: 99%

Treatment of Adult T-cell Leukemia

Uozumi

2010

J Clin Exp Hematopathol

View full text Add to dashboard Cite

show abstract

“…18 Finally, ATRA was clinically evaluated in 20 ATL patients and showed no complete remission but a partial response in 40% of the patients. 19 Even though natural retinoids have been used in APL treatment, their broad clinical use has been hampered by side effects and resistance. In addition, retinoid receptor signaling pathway is deregulated in several cancers, making tumor cells resistant to natural retinoids.…”

Section: Introductionmentioning

confidence: 99%

“…20,21 Thus, synthetic retinoids were developed with increased specificity and decreased toxicity. One promising compound is the synthetic adamantly retinoid, ST1926 (2E)-3-[39-(1-adamantyl)-49-hydroxy [1,19-biphenyl]-4-yl]-2-propenoic acid, an analog of CD437 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid. 22 ST1926 showed potential efficacy in solid tumors and hematological malignancies with minimal side effects.…”

Section: Introductionmentioning

confidence: 99%

Preclinical efficacy of the synthetic retinoid ST1926 for treating adult T-cell leukemia/lymphoma

Hajj¹,

Khalil²,

Ghandour

et al. 2014

Blood

View full text Add to dashboard Cite

show abstract

“…Importantly, clinical responses to retinoids have been reported in various T-cell malignancies, including PTCL, CTCL, and adult T-cell leukemia (ATL) [9–12, 19–22]. For example, Cheng et al reported 5 complete responses and one partial response among 12 PTCL patients treated with 13-cis retinoic acids [12].…”

Section: Discussionmentioning

confidence: 99%

Retinoic acid receptor alpha drives cell cycle progression and is associated with increased sensitivity to retinoids in T-cell lymphoma

et al. 2017

View full text Add to dashboard Cite

Peripheral T-cell lymphomas (PTCLs) are aggressive non-Hodgkin lymphomas with generally poor outcomes following standard therapy. Few candidate therapeutic targets have been identified to date. Retinoic acid receptor alpha (RARA) is a transcription factor that modulates cell growth and differentiation in response to retinoids. While retinoids have been used to treat some cutaneous T-cell lymphomas (CTCLs), their mechanism of action and the role of RARA in CTCL and other mature T-cell lymphomas remain poorly understood. After identifying a PTCL with a RARAR394Q mutation, we sought to characterize the role of RARA in T-cell lymphoma cells. Overexpressing wild-type RARA or RARAR394Q significantly increased cell growth in RARAlow cell lines, while RARA knockdown induced G1 arrest and decreased expression of cyclin-dependent kinases CDK2/4/6 in RARAhigh cells. The retinoids, AM80 (tamibarotene) and all-trans retinoic acid, caused dose-dependent growth inhibition, G1 arrest, and CDK2/4/6 down-regulation. Genes down-regulated in transcriptome data were enriched for cell cycle and G1-S transition. Finally, RARA overexpression augmented chemosensitivity to retinoids. In conclusion, RARA drives cyclin-dependent kinase expression, G1-S transition, and cell growth in T-cell lymphoma. Synthetic retinoids inhibit these functions in a dose-dependent fashion and are most effective in cells with high RARA expression, indicating RARA may represent a therapeutic target in some PTCLs.

show abstract

Clinical efficacy of all-trans retinoic acid for treating adult T cell leukemia

Abstract: These results indicated that ATRA might be a useful agent for the safe treatment of ATL.

Cited by 26 publications

References 20 publications

Treatment of Adult T-cell Leukemia

Treatment of Adult T-cell Leukemia

Preclinical efficacy of the synthetic retinoid ST1926 for treating adult T-cell leukemia/lymphoma

Retinoic acid receptor alpha drives cell cycle progression and is associated with increased sensitivity to retinoids in T-cell lymphoma

Contact Info

Product

Resources

About