Future Perspectives on Drug Targeting in Adult T Cell Leukemia-Lymphoma

Marino-Merlo, Francesca; Mastino, Antonio; Grelli, Sandro; Hermine, Olivier; Bazarbachi, Ali; Macchi, Beatrice

doi:10.3389/fmicb.2018.00925

Cited by 10 publications

(6 citation statements)

References 55 publications

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“…With the life prognosis of ATL patients improving in recent years due to improvements in treatment (Hermine et al, 2018; Marino-Merlo et al, 2018), ophthalmologists are increasingly likely to encounter opportunities to provide medical care to ATL patients. Ophthalmologists should keep in mind the high rates of intraocular infiltration and CMVR when examining patients with ATL.…”

Section: Discussionmentioning

confidence: 99%

Adult T-Cell Leukemia/Lymphoma-Related Ocular Manifestations: Analysis of the First Large-Scale Nationwide Survey

et al. 2019

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Adult T-cell leukemia/lymphoma (ATL) is a rare and aggressive T-cell malignancy with a high mortality rate, resulting in a lack of information among ophthalmologists. Here, we investigated the state of ophthalmic medical care for ATL and ATL-related ocular manifestations by conducting the first large-scale nationwide survey in Japan. A total of 115 facilities were surveyed, including all university hospitals in Japan that were members of the Japanese Ophthalmological Society and regional core facilities that were members of the Japanese Ocular Inflammation Society. The collected nationwide data on the state of medical care for ATL-related ocular manifestations and ATL-associated ocular findings were categorized, tallied, and analyzed. Of the 115 facilities, 69 (60%) responded. Overall, 28 facilities (43.0%) had experience in providing ophthalmic care to ATL patients. ATL-related ocular manifestations were most commonly diagnosed “based on blood tests and characteristic ophthalmic findings.” By analyzing the 48 reported cases of ATL-related ocular manifestations, common ATL-related ocular lesions were intraocular infiltration (22 cases, 45.8%) and opportunistic infections (19 cases, 39.6%). All cases of opportunistic infection were cytomegalovirus retinitis. Dry eye (3 cases, 6.3%), scleritis (2 cases, 4.2%), uveitis (1 case, 2.1%), and anemic retinopathy (1 case, 2.1%) were also seen. In conclusion, intraocular infiltration and cytomegalovirus retinitis are common among ATL patients, and ophthalmologists should keep these findings in mind in their practice.

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Section: Discussionmentioning

confidence: 99%

Adult T-Cell Leukemia/Lymphoma-Related Ocular Manifestations: Analysis of the First Large-Scale Nationwide Survey

et al. 2019

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“…However, more recent studies suggest primary benefit in non-lymphomatous subtypes; unfortunately, most patients inevitably relapse and require cytotoxic therapy. 14,15 Allogeneic HCT remains the only curative option for chemotherapy-sensitive disease with 1-year OS of 20% to 30%. [16][17][18] Other North American physicians perform allogeneic HCT in 2% to 11% of their patients with ATL.…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Outcomes of Caribbean Patients With Adult T-Cell Lymphoma/Leukemia at Two Affiliated New York City Hospitals

Chiu

Samra

Tam

et al. 2020

JCO Global Oncology

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PURPOSE Adult T-cell lymphoma/leukemia (ATL) is a rare and aggressive peripheral T-cell malignancy caused by human T-cell lymphotropic virus-1 infection, which occurs in areas of high prevalence, predominantly in Japan and the Caribbean basin. Most ATL literature is derived from Japan and little is published about Caribbean patients. We describe the clinicopathologic characteristics and treatment outcomes of our Caribbean patients who have ATL at the State University of New York Downstate Medical Center and Kings County Hospital. PATIENTS AND METHODS We conducted a retrospective analysis of our patients with ATL who were diagnosed between 2005 and 2017. Medical records were reviewed for clinicopathologic data and treatment outcomes. The final analysis included acute and lymphomatous subtypes only. For the univariable analysis, outcomes were calculated by using a log-rank test, and survival curves were estimated by the Kaplan-Meier method. RESULTS We identified 63 patients with acute (55%) and lymphomatous (45%) subtypes, 95% of whom had Ann Arbor stage III to IV disease. The median age was 54 years, and the study population was predominantly female (65%). Most patients (82%) received first-line etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone (EPOCH) or cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) chemotherapy (10%) with an overall response rate of 46%. The median overall survival was 5.5 months, and the median progression-free survival was 4 months. Incidence of atypical immunophenotype (32%) was higher than previously reported in the Japanese literature and was associated with worse survival ( P = .04). Abnormal cytogenetics correlated with shorter progression-free survival ( P < .05). CONCLUSION We describe here the clinicopathologic characteristics and treatment outcomes of our Caribbean patients with aggressive ATL, which is largely chemotherapy resistant, and the challenges of treating a population with unmet medical needs.

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“…The HTLV-1 infection of CD4 + lymphocytes (to a lesser degree CD8+) is associated with clonal expansion and adult T-cell leukemia/lymphoma, a very aggressive and often treatment refractory form of cancer or tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). Both have a very poor disease prognosis and efficient targeted therapy still remains a challenge (87). Given the similarities between the two viruses, it was hypothesized that HIV-1 IN inhibitors can also function as HTLV-1 IN inhibitors.…”

Section: Hiv-1 In Inhibitors Interfere With Various Polynucleotidyl Tmentioning

confidence: 99%

HIV‑1 integrase inhibitors targeting various DDE transposases: Retroviral integration versus RAG‑mediated recombination (Review)

Musat

Niţulescu

Surleac³

et al. 2019

Mol Med Report

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Transposases are ubiquitous mobile genetic elements responsible for genome development, driving rearrangements, such as insertions, deletions and translocations. across species evolution, some transposases are tamed by their host and are made part of complex cellular systems. The proliferation of retroviruses is also dependent on transposase related enzymes termed integrases. recombination-activating gene protein (raG)1 and metnase are just two examples of transposase domestication and together with retroviral integrases (ins), they belong to the dde polynucleotidyl transferases superfamily. They share mechanistic and structural features linked to the rnase H-like fold, harboring a dde(d) metal dependent catalytic motif. recent antiretroviral compounds target the catalytic domain of integrase, but they also have the potential of inhibiting other related enzymes. in this review, we report the activity of different classes of integrase inhibitors on various dde transposases. computational simulations are useful to predict the extent of off-target activity and have been employed to study the interactions between raG1 recombinase and compounds from three different pharmacologic classes. We demonstrate that strand-transfer inhibitors display a higher affinity towards the raG1 rnase H domain, as suggested by experimental data compared to allosteric inhibitors. While interference with raG1 and 2 recombination is associated with a negative impact on immune function, the inhibition of metnase or HTlV-1 integrase opens the way for the development of novel therapies for refractory cancers. Contents 1. introduction 2. docking simulations and conformations 3. recombination protein raG: a domesticated transposase 4. raG recombination versus retroviral integration 5. in inhibitors 6. HiV-1 in inhibitors potentially interfere with raGmediated recombination 7. docking simulations of in inhibitors on raG1 dimer 8. HiV-1 in inhibitors interfere with various polynucleotidyl transferases 9. conclusions

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Future Perspectives on Drug Targeting in Adult T Cell Leukemia-Lymphoma

Cited by 10 publications

References 55 publications

Adult T-Cell Leukemia/Lymphoma-Related Ocular Manifestations: Analysis of the First Large-Scale Nationwide Survey

Adult T-Cell Leukemia/Lymphoma-Related Ocular Manifestations: Analysis of the First Large-Scale Nationwide Survey

Clinical Characteristics and Outcomes of Caribbean Patients With Adult T-Cell Lymphoma/Leukemia at Two Affiliated New York City Hospitals

HIV‑1 integrase inhibitors targeting various DDE transposases: Retroviral integration versus RAG‑mediated recombination (Review)

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