Effects of combinations of therapeutic agents on the proliferation of progenitor cells in chronic myeloid leukaemia.
Combination of STI571, a tyrosine kinase inhibitor, with other drugs may be beneficial in the treatment of chronic myeloid leukaemia (CML). We measured the effects of STI571, AG490, farnesyltransferase inhibitor (FTI), interferon alpha (IFN-alpha), cytosine arabinoside (Ara-C) and all-trans retinoic acid (ATRA), singly and in combination, on clonogenic leukaemic cell proliferation. STI571, IFN-alpha and ATRA each reduced proliferation by 50-60%; AG490, FTI and Ara-C had less effect. Comparing the observed and expected (i.e. additive) effects of drug combinations showed STI571 + FTI, STI571 + AG490 and IFN-alpha + ATRA were additive; STI571 + IFN-alpha, IFN-alpha + Ara-C and STI571 + AG490 + FTI were less than additive. Thus, STI571 + FTI, STI571 + AG490 and IFN-alpha + ATRA may be better combination therapies for CML than STI571 + IFN-alpha, IFN-alpha + Ara-C or STI571 + AG490 + FTI.
Marley
Stephen B
SB
Leukaemia Research Fund Centre for Adult Leukaemia, Department of Haematology, Imperial College School of Medicine, London, UK. s.marley@ic.ac.uk
Davidson
R John
RJ
Goldman
John M
JM
Gordon
Myrtle Y
MY
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D001549:Benzamides; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D051231:Farnesyltranstransferase; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology*; D010879:Piperazines; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology*; D014212:Tretinoin / Q000627:therapeutic use; D020032:Tyrphostins / Q000627:therapeutic use
D001549:Benzamides; D004791:Enzyme Inhibitors; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D003561:Cytarabine; D014212:Tretinoin; D000068877:Imatinib Mesylate; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D011505:Protein-Tyrosine Kinases