Arsenic trioxide and methylprednisolone use different signal transduction pathways in leukemic differentiation
Küçük Resim Yok
Tarih
2002
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Pergamon-Elsevier Science Ltd
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Certain cell lines like HL 60 and K 562 are utilised as leukemic cell models for leukemogenesis research, which differentiate along the Granulocytic and/or monocytic pathway when treated with certain inducer molecules. High dose methylprednisolone treatment has been shown to induce in vivo and in vitro differentiation of myeloid leukemia cells to mature granulocytes in patients with acute promyelocytic leukemia (APL) and other subtypes of acute myeloid leukemia (AML). Arsenic trioxide (As2O3) has been confirmed to have remission induction effects on APL. However, there are conflicting results on the effects with other AML subtypes. Also. it has been well established that the reversible phosphorylation of proteins is a major regulatory mechanism in the signal transduction pathways that control cell growth and differentiation. Serine/threonine protein phosphatases (PP) are major components of phosphorylation. In this study, we investigated the effect of As,03 on HL 60 and K 562 myeloid leukemic differentiation and compared the signalling cascades of the two inducers with respect to serine/threonine PP 1 and 2A. We utilised PP1 and PP2A inhibitors okadaic acid and calyculin A. In contrast to methylprednisolone, there was no effect of phosphatase inhibitors on As2O3-induced leukemic differentiation. Incomplete leukemic differentiation occurred with lower As2O3 concentration as 10(-6) M. Unlike As2O3, methylprednisolone induced complete granulocytic and/or monocytic differentiation of HL 60 and K 562 cells via Upregulation of PP2A regulatory Subunits. Therefore, As2O3 and methylprednisolone are promising agents that have the potential to be used together in myeloid leukemic differentiation therapy. (C) 2002 Elsevier Science Ltd. All rights reserved.
Açıklama
Anahtar Kelimeler
arsenic trioxide, leukemic differentiation, protein phosphatases, methylprednisolone
Kaynak
Leukemia Research
WoS Q Değeri
Q2
Scopus Q Değeri
N/A
Cilt
26
Sayı
4
