PMID- 11233781
OWN - NLM
STAT- MEDLINE
DCOM- 20010322
LR  - 20190921
IS  - 0939-5555 (Print)
IS  - 0939-5555 (Linking)
VI  - 80
IP  - 1
DP  - 2001 Jan
TI  - Predominantly BCR-ABL negative myeloid precursors in interferon-alpha treated 
      chronic myelogenous leukemia: a follow-up study of peripheral blood 
      colony-forming cells with fluorescence in situ hybridization.
PG  - 9-16
AB  - The mechanism and target cell of the life-prolonging effect of interferon-alpha 
      (IFN-alpha) in chronic myelogenous leukemia (CML) are controversial. We studied 
      the influence of IFN-alpha treatment on the frequency of malignant hematopoietic 
      precursor cells in the peripheral blood (PB) of CML patients during the course of 
      the disease. PB 10-day colony-forming cells (PB-CFCs) were assessed with regard 
      to their quantity, lineage distribution, and BCR-ABL status, as determined by 
      fluorescence in situ hybridization (FISH). PB-CFC numbers were determined in 39 
      patients (29 in the chronic phase, 6 in an advanced stage, and 4 with progression 
      to an advanced stage during follow-up). Thirty-one patients were evaluated either 
      once or several times to determine the BCR-ABL status of the colonies. BCR-ABL 
      negative PB-CFCs were detectable at diagnosis in 5 of 11 patients. A major 
      reduction of BCR-ABL positive colonies to <25% of PB-CFCs was observed in 10/13 
      determinable IFN-alpha treated patients in early and late chronic phases, 
      indicating a high proportion of BCR-ABL negativity at the clonogenic cell level. 
      In contrast, only 3 of these patients had a cytogenetic response of <25% 
      Philadelphia chromosome (Ph1)-positive metaphases in bone marrow cytogenetics. 
      Treatment with IFN-alpha and/or hydroxyurea (HU) during chronic phase was 
      accompanied by a reduction of PB-CFCs to subnormal levels (median 24 CFCs/ml) 
      compared to controls (median 207 CFCs/ml), untreated patients in chronic phase 
      (median 25,979 CFCs/ml), and patients with advanced disease (median 6,047 
      CFCs/ml). In blast crisis (6 patients), all colonies tested were BCR-ABL 
      positive. Our results show that IFN-alpha treatment leads to a marked reduction 
      of malignant myeloid precursor cells in the PB of CML patients, which exceeds the 
      degree of cytogenetic remission. This offers an explanation for the good 
      therapeutic efficacy and even life-prolonging effect of IFN-alpha, which is also 
      observed in cytogenetic non-responders.
FAU - Sick, C
AU  - Sick C
AD  - Katharina-Kasper-Kliniken, St. Marienkrankenhaus, Medizinische Klinik, Frankfurt, 
      Germany. sick@rumms.uni-mannheim.de
FAU - Schultheis, B
AU  - Schultheis B
FAU - Pasternak, G
AU  - Pasternak G
FAU - Kottke, I
AU  - Kottke I
FAU - Horner, S
AU  - Horner S
FAU - Heissig, B
AU  - Heissig B
FAU - Hehlmann, R
AU  - Hehlmann R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Ann Hematol
JT  - Annals of hematology
JID - 9107334
RN  - 0 (Interferon-alpha)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Fusion Proteins, bcr-abl/*blood/genetics
MH  - Hematopoietic Stem Cells/drug effects
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Interferon-alpha/*therapeutic use
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy/genetics/pathology
MH  - Longitudinal Studies
EDAT- 2001/03/10 10:00
MHDA- 2001/03/27 10:01
CRDT- 2001/03/10 10:00
PHST- 2001/03/10 10:00 [pubmed]
PHST- 2001/03/27 10:01 [medline]
PHST- 2001/03/10 10:00 [entrez]
AID - 10.1007/s002770000237 [doi]
PST - ppublish
SO  - Ann Hematol. 2001 Jan;80(1):9-16. doi: 10.1007/s002770000237.