Differential control of G0 programme in chronic lymphocytic leukaemia

A novel prognostic factor

Alexey Danilov, Andreas K. Klein, Henry J. Lee, Diana Velez Baez, Brigitte T. Huber

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Chronic lymphocytic leukaemia (CLL) is a unique malignancy where quiescent B cells accumulate in the peripheral blood. Since clinical outcomes in CLL are very heterogeneous, it is of utmost importance to correctly assess the disease prognosis in each individual case. Recently, it has been shown that high ZAP-70 [Zeta-chain (T-cell receptor) associated protein kinase (70 kDa)] expression level strongly correlates with lack of IgVH mutations and poor prognosis in B-CLL. As CLL malignant cells are arrested in G0, we investigated whether Dipeptidyl Peptidase 2 (DPP2), a serine protease that plays a key role in keeping cells in the quiescent state, is involved in cell-cycle control in CLL. We have previously shown that specific inhibition of DPP2 results in apoptosis of normal lymphocytes. In this study, cell apoptosis experiments were conducted in 38 patients with B-CLL. Two distinct subsets of B-CLL were identified, susceptible and resistant to DPP2-inhibition-induced apoptosis. If resistant to apoptosis (42.1%), the CLL cells have higher expression of ZAP-70 and exhibit a worse prognosis, such as shorter treatment-free time period. Thus, resistance vs. susceptibility to DPP2-inhibiton induced apoptosis can be employed as a novel prognostic factor in CLL.

Original languageEnglish (US)
Pages (from-to)472-481
Number of pages10
JournalBritish Journal of Haematology
Volume128
Issue number4
DOIs
StatePublished - Feb 2005
Externally publishedYes

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Apoptosis
Serine Proteases
T-Cell Antigen Receptor
Cell Cycle Checkpoints
Protein Kinases
B-Lymphocytes
Lymphocytes
Mutation

Keywords

  • Apoptosis
  • Cell cycle
  • Chronic lymphocytic leukaemia

ASJC Scopus subject areas

  • Hematology

Cite this

Differential control of G0 programme in chronic lymphocytic leukaemia : A novel prognostic factor. / Danilov, Alexey; Klein, Andreas K.; Lee, Henry J.; Baez, Diana Velez; Huber, Brigitte T.

In: British Journal of Haematology, Vol. 128, No. 4, 02.2005, p. 472-481.

Research output: Contribution to journalArticle

Danilov, Alexey ; Klein, Andreas K. ; Lee, Henry J. ; Baez, Diana Velez ; Huber, Brigitte T. / Differential control of G0 programme in chronic lymphocytic leukaemia : A novel prognostic factor. In: British Journal of Haematology. 2005 ; Vol. 128, No. 4. pp. 472-481.
@article{600f3248a57749e5a2f7d9f3a7dcb016,
title = "Differential control of G0 programme in chronic lymphocytic leukaemia: A novel prognostic factor",
abstract = "Chronic lymphocytic leukaemia (CLL) is a unique malignancy where quiescent B cells accumulate in the peripheral blood. Since clinical outcomes in CLL are very heterogeneous, it is of utmost importance to correctly assess the disease prognosis in each individual case. Recently, it has been shown that high ZAP-70 [Zeta-chain (T-cell receptor) associated protein kinase (70 kDa)] expression level strongly correlates with lack of IgVH mutations and poor prognosis in B-CLL. As CLL malignant cells are arrested in G0, we investigated whether Dipeptidyl Peptidase 2 (DPP2), a serine protease that plays a key role in keeping cells in the quiescent state, is involved in cell-cycle control in CLL. We have previously shown that specific inhibition of DPP2 results in apoptosis of normal lymphocytes. In this study, cell apoptosis experiments were conducted in 38 patients with B-CLL. Two distinct subsets of B-CLL were identified, susceptible and resistant to DPP2-inhibition-induced apoptosis. If resistant to apoptosis (42.1{\%}), the CLL cells have higher expression of ZAP-70 and exhibit a worse prognosis, such as shorter treatment-free time period. Thus, resistance vs. susceptibility to DPP2-inhibiton induced apoptosis can be employed as a novel prognostic factor in CLL.",
keywords = "Apoptosis, Cell cycle, Chronic lymphocytic leukaemia",
author = "Alexey Danilov and Klein, {Andreas K.} and Lee, {Henry J.} and Baez, {Diana Velez} and Huber, {Brigitte T.}",
year = "2005",
month = "2",
doi = "10.1111/j.1365-2141.2004.05346.x",
language = "English (US)",
volume = "128",
pages = "472--481",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Differential control of G0 programme in chronic lymphocytic leukaemia

T2 - A novel prognostic factor

AU - Danilov, Alexey

AU - Klein, Andreas K.

AU - Lee, Henry J.

AU - Baez, Diana Velez

AU - Huber, Brigitte T.

PY - 2005/2

Y1 - 2005/2

N2 - Chronic lymphocytic leukaemia (CLL) is a unique malignancy where quiescent B cells accumulate in the peripheral blood. Since clinical outcomes in CLL are very heterogeneous, it is of utmost importance to correctly assess the disease prognosis in each individual case. Recently, it has been shown that high ZAP-70 [Zeta-chain (T-cell receptor) associated protein kinase (70 kDa)] expression level strongly correlates with lack of IgVH mutations and poor prognosis in B-CLL. As CLL malignant cells are arrested in G0, we investigated whether Dipeptidyl Peptidase 2 (DPP2), a serine protease that plays a key role in keeping cells in the quiescent state, is involved in cell-cycle control in CLL. We have previously shown that specific inhibition of DPP2 results in apoptosis of normal lymphocytes. In this study, cell apoptosis experiments were conducted in 38 patients with B-CLL. Two distinct subsets of B-CLL were identified, susceptible and resistant to DPP2-inhibition-induced apoptosis. If resistant to apoptosis (42.1%), the CLL cells have higher expression of ZAP-70 and exhibit a worse prognosis, such as shorter treatment-free time period. Thus, resistance vs. susceptibility to DPP2-inhibiton induced apoptosis can be employed as a novel prognostic factor in CLL.

AB - Chronic lymphocytic leukaemia (CLL) is a unique malignancy where quiescent B cells accumulate in the peripheral blood. Since clinical outcomes in CLL are very heterogeneous, it is of utmost importance to correctly assess the disease prognosis in each individual case. Recently, it has been shown that high ZAP-70 [Zeta-chain (T-cell receptor) associated protein kinase (70 kDa)] expression level strongly correlates with lack of IgVH mutations and poor prognosis in B-CLL. As CLL malignant cells are arrested in G0, we investigated whether Dipeptidyl Peptidase 2 (DPP2), a serine protease that plays a key role in keeping cells in the quiescent state, is involved in cell-cycle control in CLL. We have previously shown that specific inhibition of DPP2 results in apoptosis of normal lymphocytes. In this study, cell apoptosis experiments were conducted in 38 patients with B-CLL. Two distinct subsets of B-CLL were identified, susceptible and resistant to DPP2-inhibition-induced apoptosis. If resistant to apoptosis (42.1%), the CLL cells have higher expression of ZAP-70 and exhibit a worse prognosis, such as shorter treatment-free time period. Thus, resistance vs. susceptibility to DPP2-inhibiton induced apoptosis can be employed as a novel prognostic factor in CLL.

KW - Apoptosis

KW - Cell cycle

KW - Chronic lymphocytic leukaemia

UR - http://www.scopus.com/inward/record.url?scp=14144249579&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14144249579&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2141.2004.05346.x

DO - 10.1111/j.1365-2141.2004.05346.x

M3 - Article

VL - 128

SP - 472

EP - 481

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 4

ER -