Panobinostat (LBH589) increase survival in adult xenografic model of acute lymphoblastic leukemia with t(4;11) but promotes antagonistic effects in combination with MTX and 6MP.

Autor: Moreno DA; Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, São Paulo, CEP 14784 400, Brazil. daniellmoreno@gmail.com., Junior HLR; Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, São Paulo, CEP 14784 400, Brazil., Laranjeira ABA; Boldrini Child Center, Campinas, SP, Brazil., Cruzeiro GAV; Pediatrics Department of Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Borges KS; Genetics Department of Medical School of Ribeirão Preto, Ribeirão Preto, SP, Brazil., Salomão KB; Genetics Department of Medical School of Ribeirão Preto, Ribeirão Preto, SP, Brazil., Ramalho FS; Pathology Department of Medical School of Ribeirão Preto, Ribeirão Preto, SP, Brazil., Yunes JA; Boldrini Child Center, Campinas, SP, Brazil., Silva CLA; Hemocentro Foundation of Ribeirão Preto, Ribeirão Preto, SP, Brazil., Rego EM; Hemocentro Foundation of Ribeirão Preto, Ribeirão Preto, SP, Brazil., Scrideli CA; Pediatrics Department of Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Tone LG; Pediatrics Department of Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Jazyk: angličtina
Zdroj: Medical oncology (Northwood, London, England) [Med Oncol] 2022 Sep 29; Vol. 39 (12), pp. 216. Date of Electronic Publication: 2022 Sep 29.
DOI: 10.1007/s12032-022-01813-w
Abstrakt: Patients diagnosed with acute lymphoblastic leukemia (ALL) bearing t(4;11)/MLL-AF4 have aggressive clinical features, poor prognosis and there is an urgent need for new therapies to improve outcomes. Panobinostat (LBH589) has been identified as a potential therapeutic agent for ALL with t(4;11) and studies suggest that the antineoplastic effects are associated with reduced MLL-AF4 fusion protein and reduced expression of HOX genes. Here, we evaluated the in vitro effects of the combination of LBH589 with methotrexate (MTX) or 6-mercaptopurine (6MP) by cell proliferation assays and Calcusyn software in ALL cell line (RS4;11); the in vivo effects of LBH589 in xenotransplanted NOD-scid IL2Rgamma null mice measuring human lymphoblasts by flow cytometry; and the expression of HOX genes by qPCR after treatment in an adult model of ALL with t(4;11). LBH589 combination with MTX or 6MP did not promote synergistic effects in RS4;11 cell line. LBH589 treatment leads to increased overall survival and reduction of blasts in xenotransplanted mice but caused no significant changes in HOXA7, HOXA9, HOXA10, and MEIS1 expression. The LBH589, alone, showed promising antineoplastic effects in vivo and may represent a potential agent for chemotherapy in ALL patients with t(4;11).
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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