PMID- 12576334
OWN - NLM
STAT- MEDLINE
DCOM- 20040204
LR  - 20221109
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 101
IP  - 12
DP  - 2003 Jun 15
TI  - Persistence of malignant hematopoietic progenitors in chronic myelogenous 
      leukemia patients in complete cytogenetic remission following imatinib mesylate 
      treatment.
PG  - 4701-7
AB  - The BCR/ABL tyrosine kinase inhibitor imatinib mesylate (Gleevec, STI571; 
      Novartis, Basel, Switzerland) has shown remarkable efficacy in the treatment of 
      chronic myelogenous leukemia (CML), with a high proportion of patients achieving 
      complete cytogenetic responses (CCRs). However, it is not clear whether 
      remissions will be durable and whether imatinib mesylate can eliminate the 
      malignant primitive progenitors in which the disease arises. We investigated 
      whether residual BCR/ABL+ hematopoietic progenitors were present in patients who 
      achieved CCRs with imatinib mesylate treatment. CD34+ progenitor cells were 
      selected from bone marrow mononuclear cells (MNCs) and analyzed for the presence 
      of the BCR/ABL fusion gene by fluorescence in situ hybridization (FISH). CD34+ 
      cells were also plated in committed progenitor (colony-forming cell, or CFC) and 
      primitive progenitor (long-term bone marrow culture-initiating cell, or LTCIC) 
      cultures and resulting colonies analyzed for the presence of BCR/ABL+ cells by 
      FISH. Using these assays, residual BCR/ABL+ progenitors were detected in all 
      patients studied. Quantitative reverse transcriptase-polymerase chain reaction 
      (RT-PCR) analysis demonstrated increased levels of BCR/ABL mRNA in CD34+ cells 
      compared with total MNCs. Evaluation of samples collected at different time 
      points demonstrated persistence of BCR/ABL+ progenitors despite continued 
      treatment with imatinib mesylate. Our results indicate that inhibition of BCR/ABL 
      tyrosine kinase activity by imatinib mesylate does not eliminate malignant 
      primitive progenitors in CML patients. Patients in CCR with imatinib mesylate 
      treatment need to be followed carefully to assess for risk of relapse.
FAU - Bhatia, Ravi
AU  - Bhatia R
AD  - Division of Hematology and Bone Marrow Transplantation, City of Hope National 
      Medical Center, Duarte, CA 91010, USA. rbhatia@coh.org
FAU - Holtz, Melissa
AU  - Holtz M
FAU - Niu, Ning
AU  - Niu N
FAU - Gray, Rachel
AU  - Gray R
FAU - Snyder, David S
AU  - Snyder DS
FAU - Sawyers, Charles L
AU  - Sawyers CL
FAU - Arber, Daniel A
AU  - Arber DA
FAU - Slovak, Marilyn L
AU  - Slovak ML
FAU - Forman, Stephen J
AU  - Forman SJ
LA  - eng
GR  - CA33572/CA/NCI NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030206
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD34)
RN  - 0 (Benzamides)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 0 (RNA, Messenger)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antigens, CD34/analysis
MH  - Benzamides
MH  - Chromosomes, Human, Pair 22
MH  - Chromosomes, Human, Pair 8
MH  - Chromosomes, Human, Pair 9
MH  - Enzyme Inhibitors/*therapeutic use
MH  - Female
MH  - Fusion Proteins, bcr-abl/genetics
MH  - Hematopoietic Stem Cells/*pathology
MH  - Humans
MH  - Imatinib Mesylate
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/genetics/*pathology
MH  - Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
MH  - Male
MH  - Middle Aged
MH  - Piperazines/*therapeutic use
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors
MH  - Pyrimidines/*therapeutic use
MH  - RNA, Messenger/analysis
MH  - Remission Induction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Translocation, Genetic
MH  - Trisomy
EDAT- 2003/02/11 04:00
MHDA- 2004/02/05 05:00
CRDT- 2003/02/11 04:00
PHST- 2003/02/11 04:00 [pubmed]
PHST- 2004/02/05 05:00 [medline]
PHST- 2003/02/11 04:00 [entrez]
AID - S0006-4971(20)50627-7 [pii]
AID - 10.1182/blood-2002-09-2780 [doi]
PST - ppublish
SO  - Blood. 2003 Jun 15;101(12):4701-7. doi: 10.1182/blood-2002-09-2780. Epub 2003 Feb 
      6.