Adult T-cell leukemia cells over-express the multidrug-resistance-protein (MRP) and lung-resistance-protein (LRP) genes

Ikeda, Koki; Oka, M.; Yamada, Yasuaki; Soda, Hiroshi; Fukuda, Minoru; Kinoshita, Akitoshi; Tsukamoto, Kazuhiro; Noguchi, Yuji; Isomoto, Hajime; Takeshima, Fuminao; Murase, Kunihiko; Kamihira, Shimeru; Tomonaga, Masao; Kohno, Shigeru

doi:10.1002/(sici)1097-0215(19990812)82:4<599::aid-ijc21>3.0.co;2-r

Cited by 52 publications

(21 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…11 In fact, the overexpression of P-glycoprotein, the protein product of the multiple drug resistance gene family, and multidrugresistance protein are known to be associated with drug resistance in ATL. [10][11][12] Immunotherapy for ATL targeting cell surface components such as CD25 have shown substantial effects, but it has not been confirmed that these results are better than those after conventional chemotherapy. 18 To overcome drug resistance, high-dose chemotherapy and autologous SCT (auto-SCT) have been performed in ATL.…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4] It has a very poor prognosis [5][6][7][8] because patients are usually highly immunocompromised leading to frequent severe infections, 9 and tumor cells are usually resistant to conventional chemother- apeutic agents. [10][11][12] As there have been only a few reports of allogeneic bone marrow transplantation (allo-BMT) for ATL, [13][14][15] the outcome and any beneficial effect of allo-BMT are not yet well established. To assess the efficacy of allogeneic stem cell transplantation (allo-SCT) for ATL, we reviewed 10 cases Japanese ATL patients who had received allo-SCT.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation

Utsunomiya

Miyazaki

Takatsuka

et al. 2001

Bone Marrow Transplant

220

167

View full text Add to dashboard Cite

Summary:Adult T cell leukemia/lymphoma (ATL) is a poor prognosis T cell malignancy. In order to improve the outcome, we employed allogeneic stem cell transplantation (allo-SCT) for ATL in 10 patients, nine of whom were from HLA-identical siblings and one from an unrelated donor. Conditioning regimens varied among the patients except that all received total body irradiation. The patients tolerated the regimens well with mild, if any toxicity, and engraftment occurred in all cases. Median leukemia-free survival after allo-SCT was 17.5+ months (range 3.7-34.4+). Six of the 10 patients developed acute GVHD (one case each with grade I, III or IV, and three cases with grade II) and three patients developed extensive chronic GVHD. Four patients died after allo-SCT during the study period from either acute GVHD (grade IV), pneumonitis, gastrointestinal bleeding or renal insufficiency. Two of the 10 cases with no symptoms of GVHD relapsed with clinical ATL. These results strongly suggest that allo-SCT may improve the survival in ATL if a controlled degree of GVHD develops. Bone Marrow Transplantation (2001) 27, 15-20.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation

Utsunomiya

Miyazaki

Takatsuka

et al. 2001

Bone Marrow Transplant

220

167

View full text Add to dashboard Cite

show abstract

“…This antibody therapy was found to be effective for treating patients with ATL/ATLL (Ishida et al 2012) who have limited treatment options owing to the intrinsic resistance of ATL/ATLL cells to conventional chemotherapy (Ikeda et al 1999). However, treatment with mogamulizumab therapy (mogatherapy) has been often associated with skin eruptions as adverse effect, and a patient with ATL/ATLL with Stevens-Johnson syndrome after receiving the therapy was reported (Ishida et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Galectin-9 as a Predictive Marker for the Onset of Immune-Related Adverse Effects Associated with Anti-CCR4 MoAb Therapy in Patients with Adult T Cell Leukemia

Mohammed

Chagan-Yasutan

Ashino

et al. 2017

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Adult T-cell leukemia/lymphoma (ATL/ATLL) is one of the most malignant lymphomas with poor prognosis. ATL/ATLL cells express CC chemokine receptor 4, and mogamulizumab (anti-CCR4 monoclonal antibody) exhibits strong cytotoxicity for ATL/ATLL cells. We analyzed plasma samples of 6 patients with ATL/ATLL treated with chemotherapy followed by mogamulizumab therapy (mogatherapy) for changes in the levels of biomarkers in relation to immune-related adverse effects. As treatment is often associated with skin eruptions, we investigated the profiles of inflammatory cytokines, including galectin-9 (Gal-9), which becomes increased in various infectious diseases and allergic patients. Gal-9, soluble interleukin (IL)-2 receptor, tumor necrosis factor-α, and IL-10 levels were increased before chemotherapy, and Gal-9 levels were associated with the sIL-2 receptor, which reflects tumor burden. Inflammatory levels decreased after chemotherapy. After mogatherapy, 5 of 6 patients attained complete remission (CR), whereas 1 patient showed no response (NR) and died. Among 5 patients with CR, the biomarkers remained low during mogatherapy, except for a 3-5-fold increment in Gal-9 (associated with skin eruptions). A skin biopsy showed infiltration by inflammatory cells and Gal-9 synthesis in areas with CD8 cell infiltration. In the patient with NR, increased levels of Gal-9 and the aforementioned biomarkers were noted 3 days after mogatherapy, followed by opportunistic infections resembling immune reconstitution inflammatory syndrome. Therefore, an increased Gal-9 plasma level in ATL/ATLL indicates tumor burden and reflects immune activation by mogatherapy. These findings may indicate that an increase in the Gal-9 level, a novel immune checkpoint molecule, can reflect immune-related adverse effects of various biotherapies.

show abstract

“…2,3 This may in part be because HTLV-1 leukemic cells overexpress the multidrug resistance protein and the lungresistance protein, resulting in the pumping of a wide spectrum of agents from the plasma membrane and preventing them from entering the cytoplasm. 4,5 In addition, the down-regulation of Fas-ligand expression and rare cases of mutations in the Fas gene sequence have been reported and could also impair the induction of apoptosis through this pathway. 6 In vivo, but not in vitro, the combination of zidovudine (AZT) with interferon-␣ is a partially effective treatment that induces cell death in HTLV-1-infected cells.…”

Section: Introductionmentioning

confidence: 99%

Arsenic trioxide induces apoptosis in human T-cell leukemia virus type 1– and type 2–infected cells by a caspase-3–dependent mechanism involving Bcl-2 cleavage

Mahieux

Pise-Masison

Gessain

et al. 2001

Blood

View full text Add to dashboard Cite

IntroductionHuman T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia-lymphoma (ATLL). 1 Treatment of patients with ATLL using conventional chemotherapy has limited benefit given that HTLV-1 cells are resistant to most apoptosis-inducing agents. 2,3 This may in part be because HTLV-1 leukemic cells overexpress the multidrug resistance protein and the lungresistance protein, resulting in the pumping of a wide spectrum of agents from the plasma membrane and preventing them from entering the cytoplasm. 4,5 In addition, the down-regulation of Fas-ligand expression and rare cases of mutations in the Fas gene sequence have been reported and could also impair the induction of apoptosis through this pathway. 6 In vivo, but not in vitro, the combination of zidovudine (AZT) with interferon-␣ is a partially effective treatment that induces cell death in HTLV-1-infected cells. 7,8 In vitro, retinoic acid 9,10 or arsenic trioxide (As 2 O 3 ), in combination with IFN-␣, can also induce cell death in HTLV-1-transformed cells 11,12 through mechanisms that remain unclear but that may involve the down-regulation of NF-B in the latter case. 13 Programmed cell death, or apoptosis, consists of a highly regulated series of events allowing the organism to control cell number and tissue size. 14 It occurs in 3 phases-initiation, commitment to cell death, and execution. During apoptosis, a complex set of proteins is activated. Among them, caspases play a key role and act as initiators (for review, see 15 ). These cysteine proteases are normally present as pro-enzymes and are proteolytically cleaved to active heterodimers. They have an active-site cysteine and mediate apoptosis by proteolysis of specific substrates. Substrate specificity is determined by the 4-residue amino-terminal to the cleavage site. Caspase-dependent cleavage can either activate or inactivate the target protein. Close to 100 caspase substrates have been reported. 16 Poly (ADP-ribose) polymerase (PARP), a regulator of DNA repair, and Bcl-2 are known substrates of caspase-3. Mitochondria have been recently recognized to play a major role in the control of apoptosis or programmed cell death. 14,17 Members of the Bcl-2 family that interact with the permeability transition pore complex regulate permeabilization of mitochondrial membranes, a decisive feature of early cell death.Bcl-2 is a member of an expanding family of related proteins. Some of them are proapoptotic (Bax, Bak, Bid, Bcl-X S ) and some are antiapoptotic (Bcl-2, Bcl-X L ) (for review, see 14,18 ). It has been shown that the presence of Bcl-2 blocked the activation of caspase-3. However-and adding another level of complexityBcl-2, which inhibits cell death, can also be converted to a Bax-like death effector through its cleavage at Asp-34 by caspase-3. 19,20 Interestingly, Bcl-2 and Bcl-X L are overexpressed in HTLV-1 cells. 21,22 In the latter case, this phenomenon is linked with the constitutive activation of the NF-B pathway by Tax. 23 Tax is a 42-kd protein whose express...

show abstract

Adult T-cell leukemia cells over-express the multidrug-resistance-protein (MRP) and lung-resistance-protein (LRP) genes

Cited by 52 publications

References 16 publications

Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation

Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation

Galectin-9 as a Predictive Marker for the Onset of Immune-Related Adverse Effects Associated with Anti-CCR4 MoAb Therapy in Patients with Adult T Cell Leukemia

Arsenic trioxide induces apoptosis in human T-cell leukemia virus type 1– and type 2–infected cells by a caspase-3–dependent mechanism involving Bcl-2 cleavage

Contact Info

Product

Resources

About