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

General

Breast cancer resistance protein (BCRP/MXR/ABCG2) in adult acute lymphoblastic leukaemia: frequent expression and possible correlation with shorter disease-free survival.
Authors:	Suvannasankha, A Minderman, H O'Loughlin, KL Nakanishi, T Ford, LA Greco, WR Wetzler, M Ross, DD Baer, MR
Citation:	Suvannasankha A, etal., Br J Haematol. 2004 Nov;127(4):392-8.
RGD ID:	11081076
Pubmed:	PMID:15521915 (View Abstract at PubMed)
DOI:	DOI:10.1111/j.1365-2141.2004.05211.x (Journal Full-text)
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 (BCRP(R482)), 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.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
acute lymphoblastic leukemia	disease_progression	IEP		11081076		RGD
acute lymphoblastic leukemia	disease_progression	ISO	ABCG2 (Homo sapiens)	11081076; 11081076		RGD

Objects Annotated

Genes (Rattus norvegicus)

Abcg2 (ATP binding cassette subfamily G member 2)

Genes (Mus musculus)

Abcg2 (ATP binding cassette subfamily G member 2 (Junior blood group))

Genes (Homo sapiens)

ABCG2 (ATP binding cassette subfamily G member 2 (JR blood group))

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