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.
Granulocyte-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 (INF alpha) alone strongly inhibited CFU-GM growth in all four CML-AP/BC cases (IC50 < or = 250 IU/ml) and three out of seven CML-CP cases (IC50 < or = 500 IU/ml), but there was little or no interactive effect between various concentrations of tRA and INF alpha (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.
Sagayadan
G E
GE
Department of Oncology, Montefiore Medical Center, Albert Einstein Cancer Center, Bronx, NY 10467.
Wiernik
P H
PH
Sun
N
N
Ahearn
G
G
Thompson
D
D
Hallam
S J
SJ
Hu
X P
XP
Dutcher
J P
JP
Gallagher
R E
RE
D000328:Adult; D000368:Aged; D001483:Base Sequence; D001752:Blast Crisis / Q000473:pathology*; D005260:Female; D006098:Granulocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D014212:Tretinoin / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
D016898:Interferon-alpha; D014212:Tretinoin