Expression of lung resistance protein and correlation with other drug resistance proteins and outcome in myelodysplastic syndromes.
The major vault lung resistance protein LRP is a cytoplasmic protein involved in drug resistance, especially in acute myeloid leukemia. We looked for LRP overexpression, using immunocytochemistry with LRP 56 monoclonal antibody, on marrow slides from 41 cases of myelodysplastic syndromes (MDS). LRP overexpression (LRP+) was defined by expression of LRP 56 in at least 20% of marrow blasts. LRP overexpression was seen in 19 (46%) cases. Concordant results between LRP overexpression and P-glycoprotein (PGP) expression were seen in 66% of the cases (p = 0.03), and discordant results (LRP+ and PGP-, or LRP- and PGP+) in 33% of the cases. No correlation was seen between LRP overexpression and FAB type, karyotype, CD34, p53 expression and bcl2 overexpression in blasts. Furthermore, in the 18 cases treated with anthracycline-AraC intensive chemotherapy and the 7 cases treated with low dose AraC, the response rate was not significantly different in LRP+ and LRP- patients. Survival was also similar in LRP+ and LRP- patients. In conclusion, LRP overexpression is probably more frequent in MDS than in de novo AML and, as in AML, is only partially correlated with PGP expression. In our experience, however, LRP was not a prognostic factor for response to chemotherapy and survival in MDS.
Lepelley
P
P
Laboratorie d'Hematologie, CHU Lille, France.
Poulain
S
S
Grardel
N
N
Preudhomme
C
C
Cosson
A
A
Fenaux
P
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000208:Acute Disease; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D018952:Antigens, CD34 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology; D003613:Danazol / Q000008:administration & dosage; D018450:Disease Progression; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015993:Life Tables; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011803:Quinine / Q000494:pharmacology; D016019:Survival Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D018952:Antigens, CD34; D003561:Cytarabine; D003613:Danazol; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011803:Quinine; D016159:Tumor Suppressor Protein p53; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein