The prognostic significance of P-glycoprotein, multidrug resistance-related protein 1 and lung resistance protein in pediatric acute lymphoblastic leukemia: a retrospective study of 295 newly diagnosed patients by the Children's Oncology Group.
Multidrug resistance (MDR) is a phenomenon by which cells become resistant to an array of structurally unrelated chemotherapeutic agents. The prognostic value that P-glycoprotein (Pgp), multidrug resistance-related protein 1 (MRP1), and lung resistance protein (LRP) have in the setting of pediatric acute lymphoblastic leukemia (ALL) is controversial. In a retrospective study, we analyzed samples obtained from 295 similarly treated pediatric ALL patients to assess whether the overexpression and/or function of these proteins at diagnosis affects outcome. Most patients (70%, 207/295) did not overexpress an MDR protein. A small number of patients expressed functional Pgp (1%, 3/295) and some overexpressed functional MRP1 (10%, 19/295), with a statistically significant number of the latter being of T-lineage as opposed to pre-B (P < 0.001). A small number of patients (2%, 6/295) also overexpressed both Pgp and MRP1. Additional patients expressed increased levels of LRP. Elevated levels of these proteins at diagnosis did not correlate with risk factors and did not predict an adverse prognosis. Life-table estimates and Kaplan-Meier plots did not show any significant differences between patients who overexpressed an MDR protein compared with those who did not, nor was any difference noted when the different MDR + groups were compared with one another. These data strongly support the conclusion that the overexpression of these functional drug efflux pumps at diagnosis does not contribute to treatment failure in pediatric ALL.
Olson
Douglas P
DP
Center for Cancer and Blood Disorders, Children's National Medical Center, The George Washington University School of Medicine, Washington, DC, USA.
Taylor
Barbara J
BJ
La
Mei
M
Sather
Harland
H
Reaman
Gregory H
GH
Ivy
S Percy
SP
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000293:Adolescent; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D020394:Vault Ribonucleoprotein Particles / Q000096:biosynthesis*; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C421109:multidrug resistance-associated protein 1