Multiple resistance mechanisms in acute nonlymphoblastic leukemia (ANLL).
The expression of the resistance-related proteins P-glycoprotein 170 (P-170), glutathione-S-transferase pi (GST-pi), topoisomerase II (Topo II), thymidylate synthase (TS) and metallothionein (MT) was investigated in leukemic cells of 19 children with newly diagnosed acute nonlymphoblastic leukemia. P-170 was expressed in 84%, GST-pi in 37%, TS in 47%, MT in 68%, and Topo II was downregulated in 37% of the cases investigated. No resistance factors were found in two patients, one positive factor was found in two patients, three factors in three patients, four factors in 7 patients, and all resistance factors investigated were present in one patient. Patients who developed a relapse expressed more than two resistance mechanisms significantly more often than patients who remained in remission (p = 0.005). The probability of continuous first remission was significantly lower where more than two resistance mechanisms were expressed. The results indicate that the higher the number of resistance-related proteins in childhood ANLL the poorer the prognosis of the patients.
Sauerbrey
A
A
University of Jena, Department of Pediatrics, Jena, Germany.
Zintl
F
F
Hermann
J
J
Volm
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D018432:Drug Resistance, Multiple; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D011379:Prognosis; D012189:Retrospective Studies; D013940:Thymidylate Synthase / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008668:Metallothionein; D013940:Thymidylate Synthase; D005982:Glutathione Transferase; D004250:DNA Topoisomerases, Type II