Gene expression changes associated with progression and response in chronic myeloid leukemia

Jerald P. Radich, Hongyue Dai, Mao Mao, Vivian Oehler, Jan Schelter, Brian Druker, Charles Sawyers, Neil Shah, Wendy Stock, Cheryl L. Willman, Stephen Friend, Peter S. Linsley

Research output: Contribution to journalArticle

385 Citations (Scopus)

Abstract

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease with distinct biological and clinical features. The biologic basis of the stereotypical progression from chronic phase through accelerated phase to blast crisis is poorly understood. We used DNA microarrays to compare gene expression in 91 cases of CML in chronic (42 cases), accelerated (17 cases), and blast phase: (32 cases). Three thousand genes were found to be significantly (P <10-10) associated with phase of disease. A comparison of the gene signatures of chronic, accelerated, and blast phases suggest that the progression of chronic phase CML to advanced phase (accelerated and blast crisis) CML is a two-step rather than a three-step process, with new gene expression changes occurring early in accelerated phase before the accumulation of increased numbers of leukemia blast cells. Especially noteworthy and potentially significant in the progression program were the deregulation of the WNT/β-catenin pathway, the decreased expression of Jun B and Fos, alternative kinase deregulation, such as Arg (Abl2), and an increased expression of PRAME. Studies of CML patients who relapsed after initially successful treatment with imatinib demonstrated a gene expression pattern closely related to advanced phase disease. These studies point to specific gene pathways that might be exploited for both prognostic indicators as well as new targets for therapy.

Original languageEnglish (US)
Pages (from-to)2794-2799
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number8
DOIs
StatePublished - Feb 21 2006

Fingerprint

Blast Crisis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Gene Expression
Genes
Leukemia, Myeloid, Chronic Phase
Catenins
Hematopoietic Stem Cells
Oligonucleotide Array Sequence Analysis
Leukemia
Phosphotransferases
Therapeutics

Keywords

  • Blast crisis
  • Genetics
  • PRAME
  • Wnt

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Gene expression changes associated with progression and response in chronic myeloid leukemia. / Radich, Jerald P.; Dai, Hongyue; Mao, Mao; Oehler, Vivian; Schelter, Jan; Druker, Brian; Sawyers, Charles; Shah, Neil; Stock, Wendy; Willman, Cheryl L.; Friend, Stephen; Linsley, Peter S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 8, 21.02.2006, p. 2794-2799.

Research output: Contribution to journalArticle

Radich, JP, Dai, H, Mao, M, Oehler, V, Schelter, J, Druker, B, Sawyers, C, Shah, N, Stock, W, Willman, CL, Friend, S & Linsley, PS 2006, 'Gene expression changes associated with progression and response in chronic myeloid leukemia', Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 8, pp. 2794-2799. https://doi.org/10.1073/pnas.0510423103
Radich, Jerald P. ; Dai, Hongyue ; Mao, Mao ; Oehler, Vivian ; Schelter, Jan ; Druker, Brian ; Sawyers, Charles ; Shah, Neil ; Stock, Wendy ; Willman, Cheryl L. ; Friend, Stephen ; Linsley, Peter S. / Gene expression changes associated with progression and response in chronic myeloid leukemia. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 8. pp. 2794-2799.
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