PMID- 9324298
OWN - NLM
STAT- MEDLINE
DCOM- 19971023
LR  - 20190914
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 11
IP  - 10
DP  - 1997 Oct
TI  - Hypersensitivity of bcr-abl-positive progenitors to hyperthermia in patients with 
      chronic myeloid leukemia.
PG  - 1762-8
AB  - In this study, we evaluated the effect of hyperthermia on hematopoietic 
      progenitors from six chronic myeloid leukemia (CML) bone marrow (BM) samples at 
      diagnosis and four peripheral blood stem cell (PBSC) samples from CML patients 
      after stem cell mobilisation. CD34-positive cells, isolated from these samples, 
      were incubated for 2 h at 37, 42 or 43 degrees C and were plated in the 
      colony-forming unit granulocyte-macrophage (CFU-GM) and the long-term culture 
      initiating cell (LTCIC) assay. To evaluate purging, individual colonies from 
      these assays were analyzed for the presence of the bcr-abl gene with interphase 
      fluorescence in situ hybridization (FISH) and/or RT-PCR. BM samples showed a 
      significant higher sensitivity both at the CFU-GM and LTCIC level, after 
      treatment at 42 degrees C, as compared to the control BM samples obtained from 
      healthy volunteers. The four BM samples of CML patients with a low leukocyte 
      number at diagnosis harbored a mixture of bcr-abl-negative and positive colonies 
      and an increase in the percentage of bcr-abl-negative colonies was observed in 
      all cases. CML patients with a high leukocyte count at diagnosis, however, showed 
      only bcr-abl-positive progenitors even after hyperthermia. PBSCs showed a 
      significant higher sensitivity at the LTCIC level but not at the CFU-GM level, 
      after treatment at 42 degrees C, as compared to the control PBSC samples obtained 
      from nonhematologic cancer patients. Molecular analysis of individual colonies 
      demonstrated an increase of bcr-abl-negative progenitors after thermic treatment 
      in two out of three samples. When comparing both stem cell sources, PBSCs showed 
      a decreased thermic sensitivity as compared to the BM samples at the CFU-GM 
      level, whereas at the LTCIC level an increased thermic sensitivity was observed, 
      both for the controls and the CML samples. In conclusion, both for BM and PBSCs 
      samples, CML progenitors are more sensitive to hyperthermia than control cells, 
      especially at the LTCIC level. In agreement with these results, an increase of 
      bcr-abl-negative progenitors in six out of seven samples could be demonstrated 
      either at the CFU-GM level, LTCIC level or both. Hyperthermia should be explored 
      further as a possible purging modality in CML.
FAU - Thijsen, S F
AU  - Thijsen SF
AD  - Department of Hematology, Free University Hospital, Amsterdam, The Netherlands.
FAU - van Oostveen, J W
AU  - van Oostveen JW
FAU - Schuurhuis, G J
AU  - Schuurhuis GJ
FAU - Theijsmeijer, A P
AU  - Theijsmeijer AP
FAU - Oudejans, C B
AU  - Oudejans CB
FAU - van Wijk, I J
AU  - van Wijk IJ
FAU - Langenhuijsen, M M
AU  - Langenhuijsen MM
FAU - Ossenkoppele, G J
AU  - Ossenkoppele GJ
LA  - eng
PT  - Journal Article
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antigens, CD34)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Adult
MH  - Antigens, CD34/metabolism
MH  - Female
MH  - Fusion Proteins, bcr-abl/*metabolism
MH  - Hematopoietic Stem Cells/*cytology/*metabolism
MH  - Humans
MH  - *Hyperthermia, Induced
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*pathology
MH  - Male
MH  - Middle Aged
MH  - Sensitivity and Specificity
EDAT- 1997/10/27 00:00
MHDA- 1997/10/27 00:01
CRDT- 1997/10/27 00:00
PHST- 1997/10/27 00:00 [pubmed]
PHST- 1997/10/27 00:01 [medline]
PHST- 1997/10/27 00:00 [entrez]
AID - 10.1038/sj.leu.2400799 [doi]
PST - ppublish
SO  - Leukemia. 1997 Oct;11(10):1762-8. doi: 10.1038/sj.leu.2400799.