Progenitor cells from patients with advanced phase chronic myeloid leukaemia respond to STI571 in vitro and in vivo.
STI571 targets p210(BCR-ABL) in chronic myeloid leukaemia (CML). In vitro, STI571 reduces self-replication (replating ability) by chronic-phase CML CFU-GM. Here, we studied CFU-GM in advanced-phase (accelerated and blast crisis) CML. The numbers and self-replication of CFU-GM in advanced phase were greater than in the chronic phase. Self-replication by CFU-GM from advanced phase patients was reduced by STI571 or IFN alfa to the same extent as in the chronic phase. The reduced replating ability induced by STI571 correlated with that induced by IFN alpha (r=0.73). STI571 treatment in vivo also reduced replating ability and the numbers of CFU-GM/ml of blood.
Marley
S B
SB
Leukaemia Research Fund Centre for Adult Leukaemia, Department of Haematology, Imperial College School of Medicine, Hammersmith Campus, DuCane Road, W12 ONN, London, UK.
Davidson
R J
RJ
Lewis
J L
JL
Nguyen
D X
DX
Eades
A
A
Parker
S
S
Goldman
J M
JM
Gordon
M Y
MY
D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D019540:Area Under Curve; D001549:Benzamides; D016022:Case-Control Studies; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D016898:Interferon-alpha / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D023461:Myeloid Progenitor Cells / Q000187:drug effects; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate