PU.1 expression is restored upon treatment of chronic myeloid leukemia patients

Cancer Lett. 2008 Nov 8;270(2):328-36. doi: 10.1016/j.canlet.2008.05.024. Epub 2008 Jul 16.

Abstract

The PU.1 transcription factor is a crucial regulator of hematopoiesis which expression is altered in various leukemic processes. Our previous work in chronic myeloid leukemia (CML) cells demonstrated that interferon-alpha upregulated PU.1 expression. Here we show that expression of PU.1 is severely impaired in patients with CML at diagnosis. However, the PU.1 suppression is abrogated in patients in remission, after interferon-alpha or imatinib treatment. These effects are not found in patients with other myeloproliferative diseases such as polycythemia vera or essential thrombocythemia. PU.1 could, therefore, be used as an additional marker of the response to the treatment of the CML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / metabolism
  • Gene Expression Regulation, Leukemic / drug effects
  • Humans
  • Imatinib Mesylate
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Male
  • Mice
  • Middle Aged
  • Myeloid Cells / metabolism
  • Piperazines / therapeutic use*
  • Polycythemia Vera / genetics
  • Polycythemia Vera / metabolism
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Pyrimidines / therapeutic use*
  • RNA Interference
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Recombinant Proteins
  • Thrombocythemia, Essential / genetics
  • Thrombocythemia, Essential / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transfection
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Benzamides
  • Biomarkers, Tumor
  • Interferon alpha-2
  • Interferon-alpha
  • Piperazines
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Pyrimidines
  • RNA, Messenger
  • RNA, Small Interfering
  • Recombinant Proteins
  • Trans-Activators
  • proto-oncogene protein Spi-1
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl