Expression of a 95 kDa membrane protein is associated with low daunorubicin accumulation in leukaemic blast cells

L. A. Doyle, D. D. Ross, R. Sridhara, A. T. Fojo, Scott H Kaufmann, E. J. Lee, C. A. Schiffer

Research output: Contribution to journalArticle

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Abstract

A 95 kDa membrane protein (P-95) has been previously noted to be overexpressed in a doxorubicin-resistant subline of the MCF-7 breast cancer line and in clinical samples obtained from patients with solid tumours refractory to doxorubicin. We performed Western blotting on blast cell lysates from adults with acute myeloid leukaemia, using antisera to P-95. Concomitant flow cytometric assays measured daunorubicin accumulation and retention. Blasts from 16/46 patient samples had detectable P-95 and had reduced accumulation of daunorubicin compared with the negative marrows. Experiments with the P-95 positive MCF-7 multidrug-resistant subline demonstrated decreased daunorubicin accumulation and retention relative to the sensitive parent line. AML blast cells positive for P-95 also demonstrated greater overall in vitro survival in the presence of daunorubicin relative to the P-95-negative samples. The expression of P-95 did not correlate with failure to achieve an initial complete remission with daunorubicin and cytarabine induction chemotherapy. We conclude that the P-95 protein may possess an efflux transporter function, and may represent another mechanism responsible for anthracycline resistance in acute myeloid leukaemia.

Original languageEnglish (US)
Pages (from-to)52-58
Number of pages7
JournalBritish Journal of Cancer
Volume71
Issue number1
StatePublished - 1995
Externally publishedYes

Fingerprint

Daunorubicin
Membrane Proteins
Acute Myeloid Leukemia
Doxorubicin
Induction Chemotherapy
Anthracyclines
Cytarabine
Immune Sera
Bone Marrow
Western Blotting
Breast Neoplasms
Survival
Neoplasms
Proteins

Keywords

  • Acute mycloid leukaemia
  • Anthracycline
  • Multidrug resistance
  • Protein

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Doyle, L. A., Ross, D. D., Sridhara, R., Fojo, A. T., Kaufmann, S. H., Lee, E. J., & Schiffer, C. A. (1995). Expression of a 95 kDa membrane protein is associated with low daunorubicin accumulation in leukaemic blast cells. British Journal of Cancer, 71(1), 52-58.

Expression of a 95 kDa membrane protein is associated with low daunorubicin accumulation in leukaemic blast cells. / Doyle, L. A.; Ross, D. D.; Sridhara, R.; Fojo, A. T.; Kaufmann, Scott H; Lee, E. J.; Schiffer, C. A.

In: British Journal of Cancer, Vol. 71, No. 1, 1995, p. 52-58.

Research output: Contribution to journalArticle

Doyle, LA, Ross, DD, Sridhara, R, Fojo, AT, Kaufmann, SH, Lee, EJ & Schiffer, CA 1995, 'Expression of a 95 kDa membrane protein is associated with low daunorubicin accumulation in leukaemic blast cells', British Journal of Cancer, vol. 71, no. 1, pp. 52-58.
Doyle, L. A. ; Ross, D. D. ; Sridhara, R. ; Fojo, A. T. ; Kaufmann, Scott H ; Lee, E. J. ; Schiffer, C. A. / Expression of a 95 kDa membrane protein is associated with low daunorubicin accumulation in leukaemic blast cells. In: British Journal of Cancer. 1995 ; Vol. 71, No. 1. pp. 52-58.
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