http://www.cnr.it/ontology/cnr/individuo/prodotto/ID27459

CTLA-4 expressed by chemoresistant, as well as untreated, myeloid leukaemia cells can be targeted with ligands to induce apoptosis. (Articolo in rivista)

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CTLA-4 expressed by chemoresistant, as well as untreated, myeloid leukaemia cells can be targeted with ligands to induce apoptosis. (Articolo in rivista) (literal)

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Laurent S, Palmisano GL, Martelli AM, Kato T, Tazzari PL, Pierri I, Clavio M, Dozin B, Balbi G, Megna M, Morabito A, Lamparelli T, Bacigalupo A, Gobbi M, Pistillo MP. (2007)
CTLA-4 expressed by chemoresistant, as well as untreated, myeloid leukaemia cells can be targeted with ligands to induce apoptosis.
in British journal of haematology (Print)
(literal)

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Laurent S, Palmisano GL, Martelli AM, Kato T, Tazzari PL, Pierri I, Clavio M, Dozin B, Balbi G, Megna M, Morabito A, Lamparelli T, Bacigalupo A, Gobbi M, Pistillo MP. (literal)

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Unit of Translational Research A, National Cancer Research Institute; Department of Biology, University of Genova, Genova, Italy; Department of Human Anatomical Sciences, University of Bologna; ITOI C.N.R., Sezione di Bologna c/o IOR, Bologna, Italy; Department of Bioregulation, Institute of Medical Sciences, St Marianna University School of Medicine, Kanagawa, Japan; Service of TransfusionMedicine, S.Orsola-Malpighi Hospital, Bologna; Department of Clinical Haematology, University of Genova; Department of Haemato-Oncology, San Martino Hospital; Unit of Clinical Epidemiology, National Cancer Research Institute; Department of Oncology, Biology and Genetics, University of Genova, and Diagnostics of Lymphoproliferative Disorders, National Cancer Research Institute, Genova, Italy (literal)

Titolo

CTLA-4 expressed by chemoresistant, as well as untreated, myeloid leukaemia cells can be targeted with ligands to induce apoptosis. (literal)

Abstract

We have previously reported that about 80% of acute myeloid leukaemia (AML) samples tested at diagnosis constitutively expressed cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). The present study compared CTLA-4 expression and function of leukaemic cells from AML patients at diagnosis with those from AML patients resistant to conventional chemotherapy. We also explored the possibility of targeting CTLA-4 for apoptosis induction in chemoresistant AML cells. AML cells either from untreated patients (n = 15) or in chemoresistant phase (n = 10) were analysed for CTLA-4 protein and transcript expression by flow cytometry and reverse transcription-polymerase chain reaction respectively. CTLA-4 expression was similar in untreated and in chemoresistant samples and was not associated with patients' clinical features. In chemoresistant AML cells, CTLA-4 transduced an apoptotic signal on engagement with its recombinant ligands r-CD80 and r-CD86, which induced an average of 71% and 62% apoptotic cells, respectively, at highest concentration. Apoptosis was equally induced in untreated leukaemic cells accompanied by cleavage of procaspase-8 and -3. Thus, this study provides the first evidence that killing of leukaemic cells from AML patients may be obtained by the engagement of CTLA-4 with its ligands, opening the way to a novel potential therapeutic approach based on triggering the CTLA-4 molecule to circumvent chemoresistance in AML. (literal)

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