Breast cancer resistance protein (BCRP/MXR/ABCG2) in adult acute lymphoblastic leukaemia: Frequent expression and possible correlation with shorter disease-free survival

Attaya Suvannasankha, Hans Minderman, Kieran L. O'Loughlin, Takeo Nakanishi, Laurie A. Ford, William R. Greco, Meir Wetzler, Douglas D. Ross, Maria R. Baer

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Drugs used in treatment of adult acute lymphoblastic leukaemia (ALL) are substrates for breast cancer resistance protein (BCRP, MXR, ABCG2), which may thus play a role in resistance in this disease. Pretreatment blasts from 30 adult ALL patients were studied for BCRP mRNA by quantitative reverse transcription polymerase chain reaction analysis, BCRP protein by immunophenotyping with three antibodies and BCRP function by fumitremorgin C modulation of intracellular mitoxantrone retention, measured by flow cytometry. BCRP mRNA in all cases encoded wild type protein (BCRPR482), which mediates mitoxantrone and methotrexate resistance, but only low-level anthracycline resistance. The BXP-21, BXP-34 and anti-ABCG2 antibodies stained blasts in 13, 11 and 14 cases (43%, 37% and 47%); BXP-21 correlated well with BXP-34 and anti-ABCG2, but BXP-34 and anti-ABCG2 did not correlate, and antibody staining did not correlate with mRNA levels. BCRP function was seen in 21 cases (70%), but correlated poorly with antibody staining. An exploratory statistical analysis indicated that BXP-21 staining was predictive of shorter disease-free survival (DFS) (P = 0.0374) in this small patient population. Poor correlations between mRNA, protein and function indicate the complex biology of BCRP in adult ALL, and the possible correlation of BCRP expression with DFS should be studied in larger series.

Original languageEnglish (US)
Pages (from-to)392-398
Number of pages7
JournalBritish journal of haematology
Volume127
Issue number4
DOIs
StatePublished - Nov 2004

Keywords

  • Acute lymphoblastic leukaemia
  • Breast cancer resistance protein
  • Multidrug resistance

ASJC Scopus subject areas

  • Hematology

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