| Literature DB >> 36175721 |
Daniel Antunes Moreno1, Howard Lopes Ribeiro Junior2, Angelo Brunelli Albertoni Laranjeira3, Gustavo Alencastro Veiga Cruzeiro4, Kleiton Silva Borges5, Karina Bezerra Salomão5, Fernando Silva Ramalho6, José Andres Yunes3, Cleide Lúcia Araújo Silva7, Eduardo Magalhães Rego7, Carlos Alberto Scrideli4, Luiz Gonzaga Tone4.
Abstract
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 IL2Rgammanull 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).Entities:
Keywords: 6-Mercaptopurine; Acute lymphoblastic leukemia; Methotrexate; Panobinostat (LBH589); Xenotransplanted mice model; t(4, 11)
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Year: 2022 PMID： 36175721 DOI： 10.1007/s12032-022-01813-w
Source DB: PubMed Journal: Med Oncol ISSN： 1357-0560 Impact factor: 3.738