ZAP-70 CLL More Resistant to Apoptosis by DPP2, a Serine Protease

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Br J Haematol. 2005 Feb;128(4):472-81.

Differential control of G programme in chronic lymphocytic leukaemia:

a novel prognostic factor.

Danilov AV, Klein AK, Lee HJ, Baez DV, Huber BT.

Department of Pathology, Tufts University School of Medicine, Boston,

MA, USA.

Summary

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 IgV(H) mutations and poor prognosis

in B-CLL.

As CLL malignant cells are arrested in G(0), 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.

PMID: 15686454 [PubMed - in process]