Growth inhibition of Ph+ progenitor cells from CML patients using the tyrosine kinase inhibitor CGP57148B.
BACKGROUND
Different methods have been investigated for their purging capacity of contaminating CML cells in autologous stem cell products. CGP57148B, a tyrphostin, has been shown to be efficient in the reduction of cell proliferation of CML cell lines and primary CML cells, as well as in the inhibition of bcr/abl-related tumor formation in animal models.


METHODS
The effect of CGP57148B on purified CD34+ progenitor cells from BM, PB, or leukapheresis products of 8 CML patients was studied under serum-free cytokine-supplemented ex vivo culture conditions.


RESULTS
FISH as well as RT-PCR analysis showed a significant reduction of Ph+ cells after 7 days ex vivo-culture in the presence of the tyrphostin. Growth of Ph- cells was almost unaffected by treatment with CGP57148B.


CONCLUSIONS
Our results support the observation that CGP57148B can selectively inhibit proliferation of Ph+/bcr/abl+ primary CML cells under serum-free cytokine-supplemented culture conditions.
Waller
C F
CF
Department of Internal Medicine I-Hematology/Oncology-, Albert-Ludwigs-University, Freiburg Medical Center, Germany.
Ali
M
M
Heinzinger
M
M
Lange
W
W
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D000970:Antineoplastic Agents / Q000633:toxicity*; D001549:Benzamides; D001854:Bone Marrow Cells / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D007937:Leukapheresis; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000633:toxicity*; D011743:Pyrimidines / Q000633:toxicity*
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D001549:Benzamides; D016895:Culture Media, Serum-Free; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate