ABSTRACT
JIAN MA, SHUILIANG WANG, MING ZHAO, XIN-SHENG DENG, CHOON-KEE LEE, XIAO-DAN YU, AND BOLIN LIU
10.1 BACKGROUND
Multiple myeloma (MM) is a plasma cell malignancy characterized by specific genetic and epigenetic changes. Although many advances have been achieved in recent studies, MM remains an incurable disease and novel treatment strategies or agents are urgently needed [1,2]. A number of purine nucleoside analogs are rationally designed anticancer drugs that exert cytotoxicity via inhibition of DNA and RNA synthesis, and are currently used in the treatment of hematologic malignancies [3,4]. Cladribine (also known as 2-chlorodeoxyadenosine, 2-CDA) is an adenosine deaminase-resistant 2-deoxypurine nucleoside analog which requires phosphorylation by deoxycytidine kinase. Since this enzyme is mainly expressed in lymphocytes, cladribine is primarily active in lymphoid tissues [5]. Cladribine exerts remarkable activity in hairy cell leukemia (HCL), a chronic B-cell lymphoproliferative disorder, producing prolonged
complete remissions in most patients [6,7]. Although cladribine is particularly cytotoxic to malignant B-cells and T-cells, and is widely used in HCL [8-10], it has not been approved to treat other lymphoid malignancies. Increasing evidences suggest that cladribine administered in combination with recently approved novel agents may be a valuable and safe treatment for patients with chronic lymphocutic leukemia (CLL) [11,12] and other lymphoid disorders, such as lymphoplasmacytic lymphoma, marginal zone lymphoma, and mantle cell lymphoma [13].
