Chronic myeloid leukaemia: A paradigm shift in management.

In early 2000, a better understanding of the molecular biology of chronic myeloid leukaemia established a central role for enhanced tyrosine kinase activity leading to targeted therapy with imatinib mesylate. This paradigm shift in the management of this disease has improved the median survival from 8–9 years before 2000 to an estimated 25 years. Rapid research in this area along with well-designed multicentric clinical trials have resulted in the development of second- and third-generation tyrosine kinase inhibitors, which are more effective for patients who develop resistance to imatinib. The synergy of haematological, cytogenetic and molecular parameters is the mainstay of monitoring patients with chronic myelod leukaemia. Early identification of patients likely to have suboptimal response to initial tyrosine kinase inhibitors and when to discontinue therapy in those with an optimal response are areas of active research.

Regulatory T cells: A review.

Regulatory T cells (Tregs) play a pivotal role in the homeostasis of the immune system and in the modulation of the immune response. Tregs have emerged as key players in the development and maintenance of peripheral immune tolerance. Broadly speaking, CD4+ T cells possessing the ability to suppress immune responses can be divided into two types: naturally occurring (nTreg) and inducible (iTreg) or adaptive regulatory cells. Naturally occurring thymus-derived CD4+CD25+ Tregs are a subset of T cells which have immunosuppressive properties and are 5%–10% of the total peripheral CD4+ T cells. In normal conditions, Tregs regulate ongoing immune responses and prevent autoimmunity. Imbalanced function or number of these cells, either enhanced or decreased, might lead to tumour development and autoimmunity, respectively. These cells thus play a major role in autoimmune diseases, transplantation tolerance, infectious diseases, allergic disease and tumour immunity. These natural properties make Tregs attractive tools for novel immunotherapeutic approaches. The in vivo manipulation or depletion of Tregs may help devise effective immunotherapy for patients with cancer, autoimmunity, graftversus- host disease, infectious diseases and allergic diseases. It is crucial to understand the biology of Tregs before attempting therapies, including (i) the injection of expanded Tregs to cure autoimmune disease or prevent graft-versus-host disease or (ii) the depletion or inhibition of Tregs in cancer therapy. Recent findings in murine models and studies in humans have opened new avenues to study the biology of Tregs and their therapeutic potential. This overview provides a framework for integrating these concepts of basic and translational research.