Annu. Rev. Immunol. 2003. 21:841-894.


B CELL CHRONIC LYMPHOCYTIC LEUKEMIA: Lessons Learned from Studies of
the B Cell Antigen Receptor
Nicholas Chiorazzi1 and Manlio Ferrarini2
1North Shore–Long Island Jewish Research Institute, Manhasset, New
York 11030 email: nchizzi@...

Departments of Medicine, North Shore University Hospital and New York
University School of Medicine, Manhasset, New York 11030;

2Division of Medical Oncology C, Department of Clinical Oncology,
Istituto Nazionale per la Ricerca sul Cancro and Dipartmento di
Oncologia Clinica e Sperimentale, Universitá di Genová, Genova,
Italy; email: manlio.ferrarini@...

B cell chronic lymphocytic leukemia (B-CLL) is an accumulative
disease of slowly proliferating CD5+ B lymphocytes that develops in
the aging population. Whereas some patients with B-CLL have an
indolent course and die after many years from unrelated causes,
others progress very rapidly and succumb within a few years from this
currently incurable leukemia.

Over the past decade studies of the structure and function of the B
cell antigen receptor (BCR) used by these leukemic cells have helped
redefine the nature of this disease. In this review we summarize and
reinterpret several aspects of these BCR-related studies and how they
might relate to the disease.

In particular, we address the ability of antigens to select out and
drive B cell clones from the normal state to overt leukemic cells by
binding to BCRs that are relatively unique and characteristic of B-
CLL cells.

The differential capacity of some B-CLL cases to continue to
transduce signals through the BCR during the leukemic phase and the
consequences for the in vivo biology of the leukemic clone is also
considered.

Finally, we discuss current and emerging views of the cellular origin
of B-CLL cells and the differentiation pathways down which we believe
these cells progress.