PMID- 12816874
OWN - NLM
STAT- MEDLINE
DCOM- 20040121
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 102
IP  - 13
DP  - 2003 Dec 15
TI  - The multidrug resistance-associated protein 3 (MRP3) is associated with a poor 
      outcome in childhood ALL and may account for the worse prognosis in male patients 
      and T-cell immunophenotype.
PG  - 4493-8
AB  - The family of multidrug resistance-associated proteins (MRPs) belongs to the 
      superfamily of adenosine triphosphate-binding-cassette (ABC) transporters, which 
      have the ability to function as outward pumps for chemotherapeutic drugs and 
      therefore might be involved in drug resistance. In this study the expression of 
      the MRP2, MRP3, MRP4, MRP5, and SMRP genes was measured using TaqMan real-time 
      polymerase chain reaction (PCR) in 103 children with previously untreated acute 
      lymphoblastic leukemia (ALL) (precursor B-cell ALL [B-ALL], n = 71; T-cell ALL 
      [T-ALL], n = 32). All 5 genes were expressed with a great variability. Only MRP3 
      expression was associated with a significantly worse prognosis (P =.008). The 
      median expression of MRP3 was 10-fold higher in T-ALL than in precursor B-ALL (P 
      <.001) and 4-fold higher in male patients than in female patients (P <.001). The 
      prognostic impact of MRP3 was independent of immunophenotype or sex. Higher 
      levels of MRP3 were found in patients with a poor in vivo response to prednisone, 
      but this could not be confirmed in an independent case-control study (40 
      patients) for prednisone response. In healthy donors, the median expression of 
      MRP4 was 4-fold higher in bone marrow and 8-fold higher in CD34+ stem cells 
      compared with peripheral blood (P =.002). Our results suggest that MRP3 is 
      involved in drug resistance in childhood ALL. It therefore represents an 
      interesting target to overcome multidrug resistance. High levels of MRP3 could 
      possibly be the reason for the poorer prognosis of male patients or patients who 
      have T-ALL. Similar to other members of the family of ABC transporters, MRP4 
      seems to be a marker for immature stem cells.
FAU - Steinbach, Daniel
AU  - Steinbach D
AD  - Klinikum der FSU Jena, Klinik fur Kinder-und Jugendmedizin, Postfach, 07740 Jena, 
      Germany. daniel@steinba.ch
FAU - Wittig, Susann
AU  - Wittig S
FAU - Cario, Gunnar
AU  - Cario G
FAU - Viehmann, Susanne
AU  - Viehmann S
FAU - Mueller, Angelika
AU  - Mueller A
FAU - Gruhn, Bernd
AU  - Gruhn B
FAU - Haefer, Ralf
AU  - Haefer R
FAU - Zintl, Felix
AU  - Zintl F
FAU - Sauerbrey, Axel
AU  - Sauerbrey A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
DEP - 20030619
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - 1YV0492L5Z (multidrug resistance-associated protein 3)
SB  - IM
MH  - Adolescent
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Case-Control Studies
MH  - Child
MH  - Child, Preschool
MH  - Drug Resistance, Multiple/genetics
MH  - Drug Resistance, Neoplasm/genetics
MH  - Female
MH  - Hematopoietic Stem Cells/metabolism
MH  - Humans
MH  - Immunophenotyping
MH  - Infant
MH  - Leukemia-Lymphoma, Adult T-Cell/*blood/drug therapy/mortality
MH  - Leukocytes, Mononuclear/metabolism
MH  - Male
MH  - Multidrug Resistance-Associated Proteins/*blood/genetics
MH  - Neoplasm Proteins/*blood/genetics
MH  - Neoplastic Stem Cells/metabolism
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*blood/drug therapy/mortality
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - RNA, Messenger/blood
MH  - RNA, Neoplasm/blood
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Survival Analysis
MH  - Treatment Outcome
EDAT- 2003/06/21 05:00
MHDA- 2004/01/22 05:00
CRDT- 2003/06/21 05:00
PHST- 2003/06/21 05:00 [pubmed]
PHST- 2004/01/22 05:00 [medline]
PHST- 2003/06/21 05:00 [entrez]
AID - S0006-4971(20)43957-6 [pii]
AID - 10.1182/blood-2002-11-3461 [doi]
PST - ppublish
SO  - Blood. 2003 Dec 15;102(13):4493-8. doi: 10.1182/blood-2002-11-3461. Epub 2003 Jun 
      19.