INTRODUCTION

Any cell of the immune system (see Chapter 1, Figure 1.1) can undergo malignant transformation giving rise to leukemia, lymphoma, or myeloma. In this chapter, we focus on B-cell-type chronic lymphocytic leukemia (B-CLL), the most common leukemia in the Western Hemisphere. This B-cell lymphoproliferative disorder arises among the aging population, increasing in incidence in a linear fashion after age 50. Therefore, its incidence is likely to increase as the baby boomer generation enters the sixth decade. Because patients with the disease in general have an extended clinical course (three to twenty-five years), B-CLL is categorized as one of a group of indolent leukemias/lymphomas. However, despite progress in therapeutic strategies, B-CLL remains an incurable disease.

An abundance of new information has become available within the past decade, such that B-CLL is now divided into two related conditions, both originating from antigen selected B lymphocytes but differing in clinical course. Some patients live several decades, often without treatment, and others succumb to the disease in a few years. Here we shall discuss the possible mechanisms causing expansion and conversion of normal B lymphocytes to leukemic clones and determining the differences between the two major B-CLL subtypes. First, we will review normal B-cell development and the aberrant transformation to leukemia.

B-CELL ACTIVATION AND MATURATION

The enormous diversity of the normal B-cell-antibody repertoire initiates in the bone marrow where B lymphocytes rearrange their immunoglobulin (Ig) variable (V) region gene segments coding for the B cell's receptor for antigen (BCR) (Figures 7.1 and 7.2).