Effect of retinoic acid and interferon alpha on granulocyte-macrophage colony forming cells in chronic myeloid leukemia: Increased inhibition by all-trans- and 13-cis-retinoic acids in advanced stage disease
1994; Elsevier BV; Volume: 18; Issue: 10 Linguagem: Inglês
10.1016/0145-2126(94)90055-8
ISSN1873-5835
AutoresG Sagayadan, Peter H. Wiernik, Nancy Sun, Greg Ahearn, Deborah Thompson, Steven Hallam, Xiao Hu, Janice P. Dutcher, Robert E. Gallagher,
Tópico(s)Acute Lymphoblastic Leukemia research
ResumoGranulocyte-macrophage colony forming units (CFU-GM) from patients with advanced stage chronic myelogenous leukemia (CML), i.e. in blastic crisis (BC) or accelerated phase (AP), were inhibited by all-trans-retinoic acid (tRA) approximately 1000-fold more potently than those from chronic phase (CP) CML patients (median ic50 = 10−9 M tRA for six CML-AP/BC cases vs > 10−6 M tRA for seven CML-CP cases). A similar activity pattern was observed for the stereoisomer 13-cis-RA (cRA). There was no apparent correlation of CFU-GM retinoid sensitivity with cloning efficiency or other colony characteristics. Interferon alpha-2a (INFα) alone strongly inhibited CFU-GM growth in all four CML-AP/BC cases (ic50 ⩽ 250 IU/ml) and three out of seven CML-CP cases (ic50 ⩽ 500 IU/ml), but there was little or no interactive effect between various concentrations of tRA and INFα (50 IU/ml) on CFU-GM from either CML-AP/BC or CML-CP cases. These results suggest that CML-AP/BC CFU-GM have some intrinsic molecular alteration(s) which markedly enhances their responsiveness to tRA and cRA, which may be clinically exploitable.
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