Treatment of Refractory Peripheral T-cell Lymphoma with Denileukin Diftitox (ONTAK ® )

Talpur, Rakhshandra; Apisarnthanarax, Narin; Ward, Staci; Duvic, Madeleine

doi:10.1080/10428190210183

Cited by 57 publications

(27 citation statements)

References 11 publications

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“…Denileukin diftitox has recently been shown to be effective in both cutaneous and peripheral T-cell lymphomas. 15,42 Even though the HUT78 cells readily underwent apoptosis, at low concentrations of depsipeptide we found that there was some increase in expression of the IL-2 receptor subunits and increased sensitivity to denileukin diftitox. This may occur through increased activation of the same or of an alternate apoptotic pathway.…”

mentioning

confidence: 80%

T-cell lymphoma as a model for the use of histone deacetylase inhibitors in cancer therapy: impact of depsipeptide on molecular markers, therapeutic targets, and mechanisms of resistance

Piekarz

Robey

Zhan

et al. 2004

Blood

182

120

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Depsipeptide (FK228) is a novel histone deacetylase inhibitor currently in clinical trials and the first to demonstrate clinical activity in patients. Responses have been observed in patients with T-cell lymphomas, despite prior treatment with multiple chemotherapeutic agents. To better understand the effects of histone deacetylase inhibitors on T-cell lymphoma, the human T-cell lymphoma cell line HUT78 was tested for sensitivity and molecular response to depsipeptide. Treatment with depsipeptide, as well as other histone deacetylase inhibitors, caused induction of histone acetylation, induction of p21 expression, and substantial apoptosis without significant cell cycle arrest. Treatment with the caspase inhibitor z-VADfmk significantly inhibited depsipeptideinduced apoptosis, enabling detection of cell cycle arrest. Treatment with depsipeptide increased expression of the interleukin-2 (IL-2) receptor, and combination with the IL-2 toxin conjugate denileukin diftitox resulted in more than additive toxicity. Cells selected for resistance to depsipeptide overexpressed the multidrug resistance pump, P-glycoprotein (Pgp).However, cells selected for resistance to depsipeptide in the presence of a Pgp inhibitor had a Pgp-independent mechanism of resistance. These studies confirm the activity of depsipeptide in a T-cell lymphoma model and suggest a general sensitivity of T-cell lymphoma to histone deacetylase inhibitors, an emerging new class of anticancer agents. IntroductionThe histone deacetylase inhibitors (HDIs) are a new class of antineoplastic agents currently being evaluated in clinical trials. HDIs induce growth arrest usually associated with cellular differentiation or apoptosis. Alterations in the enzymes controlling histone acetylation and deacetylation have been shown to be a direct mechanism of transformation in some malignancies. 1 The consequence of a decrease in histone acetylation is a decreased expression of cell cycle inhibitors and other genes involved in regulating a differentiated phenotype. 2 Depsipeptide (FK228) is an HDI that has in vitro and in vivo cytotoxic activity. 3 Several families of HDIs have been characterized. These include the short-chain fatty acids, such as sodium butyrate and valproic acid; the organic hydroxamic acids, such as trichostatin A (TSA) and suberanilohydroxamic acid (SAHA); the benzamides, such as CI-994 and MS-27-275; the cyclic tetrapeptides, such as trapoxin A; and the bicyclic depsipeptides, such as depsipeptide. Similar to other HDIs, depsipeptide has been shown to induce cell cycle arrest, cellular differentiation, and apoptosis. Depsipeptide induces a p53-independent/ p21-dependent G1 arrest and a p21-independent G2/M arrest. In addition, depsipeptide causes alterations in gene expression, including increased expression of p21 and cyclin E and decreased expression of cyclin D1 and c-myc. [4][5][6] T-cell lymphomas are composed of a spectrum of clinical phenotypes ranging from low-grade, cutaneous T-cell lymphomas (CTCLs) to highly aggressive peripheral T-cell...

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mentioning

confidence: 80%

T-cell lymphoma as a model for the use of histone deacetylase inhibitors in cancer therapy: impact of depsipeptide on molecular markers, therapeutic targets, and mechanisms of resistance

Piekarz

Robey

Zhan

et al. 2004

Blood

182

120

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“…29 New drugs, such as histone deacetylase inhibitors (HDAI), bortezomib and rapamycin analogs, as well as monoclonal antibodies that specifically target T-cell markers, are also being tested. [30][31][32][33] Indeed, given that adriamycin offers little benefit to patients with T-cell lymphomas, 34 the search should continue for drugs that are active against T-cell lymphomas and that provide a more specific approach to treat this group of lymphomas.…”

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confidence: 99%

The adjusted International Prognostic Index and -2-microglobulin predict the outcome after autologous stem cell transplantation in relapsing/refractory peripheral T-cell lymphoma

Rodríguez¹,

Conde²,

Gutiérrez³

et al. 2007

Haematologica

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“…This receptor has several isoforms with the high-affinity complex comprised of three subunits, including ␣ chain (CD25), ␤ chain (CD122), and ␥-chain (CD132). DAB 389 IL-2, which preferentially targets lymphocytes bearing the high-affinity IL-2 receptor (1), has been used for treatment of mycosis fungoides (MF)/Sezary syndrome (SS) (2)(3)(4) and is in clinical trials for other T-cell and B-cell lymphoma types (5,6). Selection of suitable patients for therapy often includes pretreatment assessment of CD25 expression in tumor cells or measurement of serum IL-2 receptor levels (7).…”

Section: Introductionmentioning

confidence: 99%

Degree of CD25 Expression in T-Cell Lymphoma Is Dependent on Tissue Site

Jones

Ibrahim

Patel

et al. 2004

Clinical Cancer Research

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Purpose: Using concurrent tumor samples from different anatomical sites, we compared expression of the therapeutic targets CD25 and CD30 in T-cell lymphoma (TCL).Experimental Design: We examined levels of CD25 and CD30 by flow cytometry in tumor cells from peripheral blood and lymph node in 13 cutaneous TCL patients and by immunohistochemistry in concurrent lymph node and skin biopsy specimens in 17 additional TCL cases, mostly mycosis fungoides. Tumor cell expression was correlated with patterns of expression in nonneoplastic lymphocytes in 14 reactive lymph node and 10 skin samples showing chronic dermatitis. Expression of CD25 and CD30 in all biopsy samples was compared with that of cutaneous lymphocyte antigen (CLA), a mediator of skin homing.Results: By flow cytometry, we noted significantly decreased expression of CD25 in lymph node compared with peripheral blood in 8 of 13 TCLs, with no changes in CD30 levels in 4 cases studied. Using immunohistochemistry, CD25 was strongly expressed in epidermotropic tumor cells in 13 of 17 (76%) TCL skin specimens but was decreased in the corresponding lymph node in 12 of these cases. CD30 was expressed at roughly equal intensity in tumor cells from both sites, except in 1 case. CLA showed a similar pattern to CD25, being expressed by tumor cells in 16 of 17 (94%) skin specimens, but was largely absent in tumor cells in the corresponding lymph node in 12 of these patients. In T cells from reactive lymph node biopsy specimens, CD25 was highly expressed only in dermatopathic lymphadenitis associated with transient skin rashes.Conclusions: We demonstrate in vivo that decreased levels of CD25 expression occur in TCL when it involves lymph node, similar to what is seen with CLA. This demonstrable variation related to anatomical localization has implications for the measurement of surface expression of CD25 and for understanding the response of patients with cutaneous TCL to interleukin 2 receptor-targeted immunotherapy.

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Treatment of Refractory Peripheral T-cell Lymphoma with Denileukin Diftitox (ONTAK ® )

Cited by 57 publications

References 11 publications

T-cell lymphoma as a model for the use of histone deacetylase inhibitors in cancer therapy: impact of depsipeptide on molecular markers, therapeutic targets, and mechanisms of resistance

T-cell lymphoma as a model for the use of histone deacetylase inhibitors in cancer therapy: impact of depsipeptide on molecular markers, therapeutic targets, and mechanisms of resistance

The adjusted International Prognostic Index and -2-microglobulin predict the outcome after autologous stem cell transplantation in relapsing/refractory peripheral T-cell lymphoma

Degree of CD25 Expression in T-Cell Lymphoma Is Dependent on Tissue Site

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