Predictive value of multidrug resistance proteins and cellular drug resistance in childhood relapsed acute lymphoblastic leukemia.
OBJECTIVE
Cellular resistance in childhood acute leukemias might be related to profile and function of multidrug resistance proteins and apoptosis regulating proteins. The aims of the study were: (1) analysis of expression of MRP1, PGP1, LRP, BCL-2 and p53 proteins; (2) correlation with ex vivo drug resistance, and (3) analysis of their prognostic impact on clinical outcome in childhood acute lymphoblastic (ALL) and acute myeloid (AML) leukemia.


METHODS
Total number of 787 children diagnosed for initial ALL (n = 527), relapsed ALL (n = 104), initial AML (n = 133) and relapsed AML (n = 23) were included into the study. Mean follow-up period was 3.5 years. Drug resistance for up to 30 anticancer agents was performed by the MTT assay. Expression of all proteins was tested by flow cytometry.


RESULTS
Both initial AML and relapsed ALL samples showed higher drug resistance than initial ALL samples. No significant differences were found in drug resistance between initial and relapsed AML samples. The presence of multidrug resistance and apoptosis proteins had no impact on pDFS in iALL and iAML, however strong trend towards adverse prognostic impact of MRP1, PGP and LRP on pDFS in rALL was observed. The same trend was observed for each of analyzed co-expressions of tested multidrug resistance proteins.


CONCLUSIONS
The phenomenon of cellular drug resistance in childhood acute leukemias is multifactorial and plays an important role in response to therapy. Expression of MRP1, PGP and LRP proteins, as well as their co-expression play possible role in childhood relapsed ALL.
Styczynski
Jan
J
Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, ul. Curie-Sklodowskiej 9, 85-094, Bydgoszcz, Poland. jstyczynski@cm.umk.pl
Wysocki
Mariusz
M
Debski
Robert
R
Czyzewski
Krzysztof
K
Kolodziej
Beata
B
Rafinska
Beata
B
Kubicka
Malgorzata
M
Koltan
Sylwia
S
Koltan
Andrzej
A
Pogorzala
Monika
M
Kurylak
Andrzej
A
Olszewska-Slonina
Dorota
D
Balwierz
Walentyna
W
Juraszewska
Edyta
E
Wieczorek
Maria
M
Olejnik
Igor
I
Krawczuk-Rybak
Maryna
M
Kuzmicz
Marta
M
Kowalczyk
Jerzy
J
Stefaniak
Jolanta
J
Badowska
Wanda
W
Sonta-Jakimczyk
Danuta
D
Szczepanski
Tomasz
T
Matysiak
Michal
M
Malinowska
Iwona
I
Stanczak
Elzbieta
E
Wachowiak
Jacek
J
Konatkowska
Benigna
B
Gil
Lidia
L
Balcerska
Anna
A
Maciejka-Kapuscinska
Lucyna
L
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics / Q000378:metabolism*; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein