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Previous Volume 352:804-815 February 24, 2005 Number 8 Next

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When chronic lymphocytic leukemia (CLL) was last reviewed in the Journal,¹ it was considered a homogeneous disease of immature, immune-incompetent, minimally self-renewing B cells,² which accumulate relentlessly because of a faulty apoptotic mechanism.³ In the past decade, these views have been transformed by a wealth of new information about the leukemic cells. CLL is now viewed as two related entities, both originating from antigen-stimulated mature B lymphocytes, which either avoid death through the intercession of external signals or die by apoptosis, only to be replenished by proliferating precursor cells (Table 1).

View this table: [in this window] [in a new window]   Table 1. A Comparison of Historical and Current Views . . . [Full Text of this Article]

 
Normal B Lymphocytes

CLL and the Biology of Leukemic Lymphocytes

The Biology of Leukemic Lymphocytes and the Clinical Course of CLL

Inducing Factors in CLL

Promoting Factors in CLL

            Inferring the Role of Antigenic Stimulation from B-Cell Receptors

            Signal Transduction after Antigen Engagement

            Consequences of Signal Transduction through the B-Cell Receptor

            Signals from the Microenvironment

            Appearance and Evolution of New Genetic Mutations

A Unifying Hypothesis for the Development, Growth, and Evolution of CLL

Growth and Evolution of CLL Cells

Development of CLL from Normal B Lymphocytes

From Which Subpopulation Do CLL Cells Develop?

Clinical Implications

Prognosis

Management

New Therapeutic Approaches

Source Information

From the Institute for Medical Research, North Shore–LIJ Health System (N.C., K.R.R.), and the Departments of Medicine, North Shore University Hospital, Manhasset, N.Y., and New York University School of Medicine, New York (N.C.); the Departments of Medicine, Long Island Jewish Medical Center, New Hyde Park, N.Y., and Albert Einstein School of Medicine, Bronx, N.Y. (K.R.R.); and the Division of Medical Oncology C, Istituto Nazionale per la Ricerca sul Cancro, and the Dipartimento di Oncologia Clinica e Sperimentale, Universitá di Genova — both in Genoa, Italy (M.F.).

Address reprint requests to Dr. Chiorazzi at the Institute for Medical Research, North Shore–LIJ Health System, 350 Community Dr., Manhasset, NY 11030, or at nchizzi@nshs.edu.

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