POP and MRP overexpressions are negative prognostic factor on anll

M. Michieli, D. Damiani, R. J. Sdiepei, A. Eimaccra, A. Candoni, D. Raspadori, G. Visani, P. Masolini, A. Michehitti, L. Marin, A. Rogalo, M. Baccarani

Research output: Contribution to journalArticlepeer-review

Abstract

By flow cytometry, the P-glycoprotein (PGP), the Lung Resistance-related Protein (LRP) and the Multidrug Resistance associated Protein (MRP) expressions and the blast cells' Intracellular Daunombicin Accumulation (IDA) were evaluated in 91 de Novo Acute Non Lymphocytic Leukemias (ANLL) at onset treated with chemotherapy protocol containing Arabinosyl-Cylosine (AraC) and Idarubicin. Based on the MDR immunophenotyping performed by using the MRK-16 (anti PGP), the LRP-56 (anti LRP) and the MRProfi (anti MRP), 44/91(48%) patients were classified as PGP overexpressing (+), 42/91(46%) as LRP+ and 8/91 as MRP+. The more frequent MDR clusters were the PGP-/LRP/MRP- (30/91 cases33%) and the PGP+/LRP+/MRP- (25/91cases,27%) followed by the PGPVLRP-/MRP- (14/91) and the PGP-/LRP+/MRP(14/91).The PGP+, the LRP+ and the MRP+ cases showed a median IDA significantly lower than the respective PGP-, LRP- and MRP- cases: median DNRNMFI 202 (from 63 to 265) versus 303 (117-496) (P=.0000), 201 (107281) versus 289 (63-496) (P=.0000) and 232 (63-246) versus 257 ( 107-496) (P=.0176) respectively. Only the MRK-16 MFI showed a significant negative correlation to the IDA (P.0000, r -0.63). Both a PGP overexpression and an MRP overexpression appeared to predict a poor therapy response .In fact Primary Resistances were 22/43 (51 %) on PGP+ versus 8/47 (17 %) on PGPcases (P=.001 ) and 5/8 (63%) on MRP+ versus 21/83 (25 %) on MRP- cases (P=.046 ). Concerning the MDR clusters, as compared to the 30 PGP-/LRP/MRP- cases both the 25 PGP+/LRP-f/MRP- and the 14 PGP+/LRP-/MRPcases showed a higher frequency of resistant disease. Primary Resistances were 3/30 (10%) on the PGP-/LRP-/MRP- versus 12/25 (48%) on the PGP+/LRP+/MRP- (P=.004) and versus 7/14 (50%) on the PGP+/LRP-/MRP(P=.010 ). Only 2/14 PGP-/LRP+/MRP- cases showed a P.R. This data suggests that, on ANLL patients treated with Ara-C and Idarubicin, only a PGP and an MRP overexpression seems to predict a Primary Resistance.

Original languageEnglish
Pages (from-to)871
Number of pages1
JournalExperimental Hematology
Volume25
Issue number8
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

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