P-glycoprotein in adult hematologic malignancies.
The huge discrepancies in the proportion of tumors positive for P-gp observed in the literature limit any definite conclusions, except for the urgent need for standardized methods to compare results. It is well known by scientists that only positive results are published. For this reason, the frequency of P-gp expression in leukemia and lymphoma may be overestimated. The role of the MDR phenotype in clinical resistance is also not clearly demonstrated, because of the frequent association of other markers of bad prognosis on the same subset of cells (CD34, CD7 in leukemia). Hematologic malignancies are the most extensively studied tumors for drug resistance, and they could be a model for the therapeutic use of modifier agents. Many clinical trials are now ongoing in myeloma, acute leukemia, and lymphoma, with new modifier agents. The standardization of methods for P-gp, permitting large multicentric studies, and the results of randomized studies with modifier agents will help us know if mdr1 gene overexpression is of clinical importance in hematologic malignancies.
Marie
J P
JP
Central Laboratory of Hematology, Hôtel-Dieu, Paris, France.
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000208:Acute Disease; D000328:Adult; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002908:Chronic Disease; D018432:Drug Resistance, Multiple / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007938:Leukemia / Q000145:classification / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016896:Treatment Outcome
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C095122:multidrug resistance protein 3