PMID- 12214288
OWN - NLM
STAT- MEDLINE
DCOM- 20030716
LR  - 20191106
IS  - 0037-1963 (Print)
IS  - 0037-1963 (Linking)
VI  - 39
IP  - 3 Suppl 2
DP  - 2002 Jul
TI  - Chronic myeloid leukemia: current therapies and the potential role of 
      farnesyltransferase inhibitors.
PG  - 11-7
AB  - The treatment of patients with chronic myeloid leukemia (CML) is evolving 
      rapidly. With conventional chemotherapy the clinical course is characterized by a 
      chronic phase (median duration, 4 to 5 years), followed by an accelerated phase 
      with transition to a terminal blast crisis. Treatment with busulfan or 
      hydroxyurea does not alter the natural history. Interferon alfa (IFN-alpha) 
      prolongs life expectancy by approximately 20 months but is associated with 
      significant toxicity. Evidence indicates that bone marrow transplantation from a 
      related human leukocyte antigen (HLA)-identical donor can be curative in younger 
      patients. However, transplantation is available to only a minority of patients 
      and entails severe toxicity and transplant-related mortality. Dramatic advances 
      in the understanding of the molecular pathophysiology of CML have led to a new 
      era of targeted therapy. The specific tyrosine kinase inhibitor imatinib mesylate 
      demonstrates a high level of efficacy in CML with acceptable toxicity. 
      Farnesyltransferase inhibitors (FTIs) are another important class of targeted 
      agents with the potential to act at multiple sites within dysregulated signal 
      transduction networks. ZARNESTRA (formerly R115777, Ortho Biotech Oncology, 
      Raritan, NJ), an oral FTI, has shown activity and is well tolerated in both 
      chronic- and accelerated-phase patients. With their mechanistic specificity, the 
      new modalities offer the promise of increased antileukemic activity and an 
      improved therapeutic index.
CI  - Copyright 2002, Elsevier Science (USA). All rights reserved.
FAU - Keating, Armand
AU  - Keating A
AD  - Princess Margaret Hospital, Toronto, Ontario, Canada.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Semin Hematol
JT  - Seminars in hematology
JID - 0404514
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - EC 2.5.- (Alkyl and Aryl Transferases)
RN  - EC 2.5.1.29 (Farnesyltranstransferase)
SB  - IM
MH  - Alkyl and Aryl Transferases/antagonists & inhibitors
MH  - Animals
MH  - Antineoplastic Agents/therapeutic use
MH  - Blast Crisis/therapy
MH  - Enzyme Inhibitors/therapeutic use
MH  - Farnesyltranstransferase
MH  - Forecasting
MH  - Humans
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*therapy
RF  - 59
EDAT- 2002/09/06 10:00
MHDA- 2003/07/17 05:00
CRDT- 2002/09/06 10:00
PHST- 2002/09/06 10:00 [pubmed]
PHST- 2003/07/17 05:00 [medline]
PHST- 2002/09/06 10:00 [entrez]
AID - ashem0390011b [pii]
AID - 10.1053/shem.2002.35979 [doi]
PST - ppublish
SO  - Semin Hematol. 2002 Jul;39(3 Suppl 2):11-7. doi: 10.1053/shem.2002.35979.