Studies of some mechanisms of drug resistance in chronic myeloid leukemia (CML).
CML is the myeloproliferative disorder connected with the specific chromosome translocation (9;22) and occurrence of the fusion gene/protein BCR-ABL. BCR-ABL protein is believed to inhibit apoptosis and to cause drug resistance. We investigated the correlation of two different forms of BCR-ABL mRNA in 94 pts with their overall survival. It was found that b2a2 (but not b2a3) mRNA expression correlates with longer survival of patients treated with chemotherapy. We did not find an influence of different types of BCR/ABL mRNA on the survival of pts treated with interferon-alpha. FAS/APO-1 antigen was expressed by the cells of 34% of the pts in CML blast crisis (BC) and directly correlated with the the expression of CD34, CD13 and CD14 differentiation antigens. FAS/APO-1 non-expression correlated with higher rate of remissions in BC. We investigated P-glyco-protein (Pgp) expression and functional activity in 40 BC CML pts. 2-fold shorter survival was found in the pts with Pgp expression. Pgp expression strongly correlated with CD13 antigen. Consecutive studies of pts in BC CML show that Pgp expressing cells often do not multiply in the course of BC CML. We postulate that Pgp may be regarded as differentiation marker of the cells and the unfavorable prognostic factor in BC CML.
Turkina
A G
AG
Haematological Research Centre of Russian Academy of Medical Sciences, Moscow, Russia.
Logacheva
N P
NP
Stromskaya
T P
TP
Zabotina
T N
TN
Kuznetzov
S V
SV
Sachibzadaeva
K K
KK
Tagiev
A
A
Juravlev
V S
VS
Khoroshko
N D
ND
Baryshnikov
A Y
AY
Stavrovskaya
A A
AA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D017209:Apoptosis; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D018432:Drug Resistance, Multiple; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D019450:Genes, MDR; D006801:Humans; D016130:Immunophenotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D008297:Male; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014178:Translocation, Genetic; D019014:fas Receptor / Q000032:analysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019014:fas Receptor; D016044:Fusion Proteins, bcr-abl