Multidrug resistance in relapsed acute myeloid leukemia: Evidence of biological heterogeneity

Chirayu Patel, Leif Stenke, Sudhir Varma, Marita Lagergren Lindberg, Magnus Björkholm, Jan Sjöberg, Kristina Viktorsson, Rolf Lewensohn, Ola Landgren, Michael M. Gottesman, Jean Pierre Gillet

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

BACKGROUND Studies of mechanisms mediating resistance to chemotherapy led to the discovery of the multidrug transporter ABCB1 (ATP-binding cassette, subfamily B, member 1), often expressed in leukemic cells of patients with acute myeloid leukemia (AML). Most clinical trials evaluating the strategy of inhibiting efflux-mediated chemotherapeutic resistance have been unsuccessful, clearly indicating the need for a better approach. METHODS This study investigated the clinical relevance of 380 genes whose expression has been shown to affect the response to chemotherapy, mostly through in vitro studies, in 11 paired samples obtained at AML diagnosis and at relapse. The expression profiling of these 380 genes was performed using TaqMan-based quantitative reverse-transcription polymerase chain reaction. Patients had a median age of 58 years at diagnosis, a median duration of complete remission of 284.5 days, and a median overall survival of 563 days. Cytogenetic abnormalities were detected at diagnosis in 4 patients, whereas 5 displayed a normal karyotype and 2 were not investigated. RESULTS Hierarchical clustering shows that samples taken at diagnosis and relapse clustered in pairs for 6 patients of the 11 studied, suggesting recurrence of the same leukemic blast, whereas for the other 5 patients, the data indicate their relapse blasts arose from different origins. A patient-by-patient analysis of the paired samples led to the striking observation that each had a unique gene signature representing different mechanisms of resistance. CONCLUSIONS The data underline the need for personalized molecular analysis to tailor treatment for patients with AML.

Original languageEnglish (US)
Pages (from-to)3076-3083
Number of pages8
JournalCancer
Volume119
Issue number16
DOIs
StatePublished - Aug 15 2013
Externally publishedYes

Keywords

  • acquired drug resistance
  • acute myeloid leukemia
  • leukemia cell lines
  • multidrug resistance
  • therapy-related drug resistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Multidrug resistance in relapsed acute myeloid leukemia: Evidence of biological heterogeneity'. Together they form a unique fingerprint.

Cite this