Expression levels of Lyn, Syk, PLCγ2 and ERK in patients with chronic lymphocytic leukemia, and higher levels of Lyn are associated with a shorter treatment-free survival

Abstract

There is now strong evidence that B-cell receptor (BCR) signaling plays a major role in the development of chronic lymphocytic leukemia (CLL). The purpose of this study was to investigate the expression levels of some of the molecules involved in the signaling cascade originating from the BCR (Syk, Lyn, PLCγ2, ERK) and analyze possible correlations of mRNA levels with biological/clinical features. Our study population consisted of 92 consecutive patients with newly diagnosed CLL. Several genes of BCR signaling (Lyn, Syk, PLCγ2 and ERK) and ZAP-70 were measured by quantitative polymerase chain reaction (qPCR). The signaling molecules of BCR were strongly associated with each other, and ZAP-70 correlated well with Lyn, Syk, PLCγ2 and ERK. Associations between treatment response and Lyn, Syk, PLCγ2 and ERK were not found. Moreover, a higher level of Lyn mRNA was associated with a shorter treatment-free survival (TFS) (univariate analysis only; multivariate Cox analysis showed that only ZAP-70 and Binet stage were independent prognostic factors and associated with TFS). Though Lyn was not an independent prognostic factor, it still might be a new therapy target of CLL. BCR signaling provides perspectives for future development of an exciting new class of kinase inhibitors.

Keywords::

• Chronic leukemia lymphoma
• B-cell receptor signaling
• Lyn
• Syk
• PLCγ2
• ERK
• ZAP-70

Acknowledgements

This study was supported by the National Natural Science Foundation of China (30971296, 81170485, 81170488, 81200360), Natural Science Foundation of Jiangsu Province (BK2010584, BK2012484), Key Project of Health Department of Jiangsu Province (K201108), Jiangsu Province's Medical Elite Program (RC2011169), Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institute (JX10231801), National Public Health Grand Research Foundation (201202017), the Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU, Key Project supported by medical science and technology development Foundation of Nanjing Department of Health (ZKX09016) and the Project for State Key Clinical Department construction.

Potential conflict of interest

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