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A Distinct p53 Protein Isoform Signature Reflects the Onset of Induction Chemotherapy for Acute Myeloid Leukemia

Authors' Affiliations: ¹ Hematology Section, Institute of Medicine, University of Bergen; ² Hematology Section, Department of Internal Medicine, Haukeland University Hospital; ³ The Gade Institute, University of Bergen and Haukeland University Hospital, Bergen, Norway; and ⁴ Department of Surgery and Molecular Oncology, University of Dundee, Dundee, United Kingdom

Requests for reprints: Bjorn Tore Gjertsen, Hematology Section, Institute of Medicine, University of Bergen, N-5021 Bergen, Norway. Phone: 47-55-97-50-00; Fax: 47-55-97-29-50; E-mail: bjorn.gjertsen{at}med.uib.no.

Purpose: The antioncogene protein product p53 has not been studied previously in cancer patients during in vivo chemotherapy. This study examined the early p53 protein and gene expression during induction chemotherapy in acute myeloid leukemia (AML).

Experimental Design: Leukemic cells were collected from five AML patients during their first 18 hours of induction chemotherapy and examined for p53 protein and gene expression by one- and two-dimensional gel immunoblot and high-density gene expression arrays.

Results: Up-regulation of p53 protein expression was detected in AML patients posttreatment in vivo. One- and two-dimensional gel immunoblots showed two main forms of p53, denominated p53 and p53, both recognized by various NH₂-terminal directed antibodies. As a response to treatment, we detected rapid accumulation of p53, with significantly altered protein expression levels already after 2 hours. The accumulation of p53 was accompanied by increased transcription of putative p53 target genes and subsequent cytopenia in the patients.

Conclusion: Up-regulation of the p53 protein and target genes seems to be a prominent feature in induction chemotherapy of AML. The rapid shift from a shorter p53 protein form () toward the full-length protein () underscores the complexity of p53 protein modulation in patients undergoing chemotherapy.

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