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- Title
CTLA-4 expressed by chemoresistant, as well as untreated, myeloid leukaemia cells can be targeted with ligands to induce apoptosis.
- Authors
Laurent, Stefania; Palmisano, Giulio L.; Martelli, Alberto M.; Kato, Tomohiro; Tazzari, Pier Luigi; Pierri, Ivana; Clavio, Marino; Dozin, Beatrice; Balbi, Giuseppe; Megna, Mauro; Morabito, Anna; Lamparelli, Teresa; Bacigalupo, Andrea; Gobbi, Marco; Pistillo, Maria Pia
- 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.
- Subjects
ACUTE myeloid leukemia; APOPTOSIS; CELL death; ANTIGENS; IMMUNITY; FLOW cytometry; POLYMERASE chain reaction
- Publication
British Journal of Haematology, 2007, Vol 136, Issue 4, p597
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/j.1365-2141.2006.06472.x