Steroid effects on ZAP-70 and SYK in relation to apoptosis in poor prognosis chronic lymphocytic leukemia

Leuk Res. 2009 Oct;33(10):1335-43. doi: 10.1016/j.leukres.2009.02.022. Epub 2009 Mar 17.


There is resurgent interest in glucocorticoids (GCs) in the treatment of poor prognosis chronic lymphocytic leukemia (CLL). Little is known however on how GCs induce apoptosis in CLL. Methylprednisolone (MP) induces apoptosis in ZAP-70 positive CLL more readily than in ZAP-70 negative CLL, which is in contrast to the effects of radiation and chemotherapy. The increased GC sensitivity of ZAP-70+ CLL was studied in relation to the expression status of ZAP-70 and the related signal transducing tyrosine kinase SYK. Both ZAP-70 and SYK were downregulated by GC treatment. Moreover, SYK was dephosphorylated by the phosphatase PTP1B of which the expression and translation levels were induced by GCs. Inhibition of PTP1B successfully restored ZAP-70 expression and SYK phosphorylation but did not interfere with GC-induced apoptosis. Therefore, the downregulation of ZAP-70 and P-SYK per se during treatment with GCs is not sufficient to induce apoptosis, and different mechanisms must therefore be responsible for the increased steroid sensitivity of ZAP-70+ CLL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use*
  • Annexin A5 / metabolism
  • Apoptosis* / drug effects
  • Chlorambucil / therapeutic use
  • Down-Regulation*
  • Flow Cytometry
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Intracellular Signaling Peptides and Proteins / drug effects
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / enzymology
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Methylprednisolone / therapeutic use
  • Plasmids
  • Prognosis
  • Protein-Tyrosine Kinases / drug effects
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Syk Kinase
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use
  • ZAP-70 Protein-Tyrosine Kinase / drug effects
  • ZAP-70 Protein-Tyrosine Kinase / genetics*
  • ZAP-70 Protein-Tyrosine Kinase / metabolism


  • Adrenal Cortex Hormones
  • Annexin A5
  • Intracellular Signaling Peptides and Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Chlorambucil
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • ZAP-70 Protein-Tyrosine Kinase
  • Vidarabine
  • fludarabine
  • Methylprednisolone