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 journalArticle

56 Citations (Scopus)

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
Pages (from-to)392-398
Number of pages7
JournalBritish Journal of Haematology
Volume127
Issue number4
DOIs
StatePublished - Nov 2004

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Disease-Free Survival
Breast Neoplasms
Mitoxantrone
Messenger RNA
Staining and Labeling
Antibodies
Proteins
Immunophenotyping
Disease Resistance
Anthracyclines
Methotrexate
Reverse Transcription
Anti-Idiotypic Antibodies
Flow Cytometry
Polymerase Chain Reaction
Pharmaceutical Preparations
Population
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

Breast cancer resistance protein (BCRP/MXR/ABCG2) in adult acute lymphoblastic leukaemia : Frequent expression and possible correlation with shorter disease-free survival. / Suvannasankha, Attaya; Minderman, Hans; O'Loughlin, Kieran L.; Nakanishi, Takeo; Ford, Laurie A.; Greco, William R.; Wetzler, Meir; Ross, Douglas D.; Baer, Maria R.

In: British Journal of Haematology, Vol. 127, No. 4, 11.2004, p. 392-398.

Research output: Contribution to journalArticle

Suvannasankha, Attaya ; Minderman, Hans ; O'Loughlin, Kieran L. ; Nakanishi, Takeo ; Ford, Laurie A. ; Greco, William R. ; Wetzler, Meir ; Ross, Douglas D. ; Baer, Maria R. / Breast cancer resistance protein (BCRP/MXR/ABCG2) in adult acute lymphoblastic leukaemia : Frequent expression and possible correlation with shorter disease-free survival. In: British Journal of Haematology. 2004 ; Vol. 127, No. 4. pp. 392-398.
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