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Prepublished online as a Blood First Edition Paper on September 12, 2002; DOI 10.1182/blood-2002-07-2009.
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Blood, 15 February 2003, Vol. 101, No. 4, pp. 1220-1235
REVIEW ARTICLE
Cell cycle deregulation in B-cell lymphomas
Margarita Sánchez-Beato,
Abel Sánchez-Aguilera, and
Miguel A. Piris
From the Lymphoma Group, Molecular Pathology Program,
Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid,
Spain.
Disruption of the physiologic balance between cell proliferation
and death is a universal feature of all cancers. In general terms,
human B-cell lymphomas can be subdivided into 2 main groups, low- and
high-growth fraction lymphomas, according to the mechanisms through
which this imbalance is achieved. Most types of low-growth fraction
lymphomas are initiated by molecular events resulting in the inhibition
of apoptosis, such as translocations affecting BCL2, in
follicular lymphoma, or BCL10 and API2/MLT1, in
mucosa-associated lymphoid tissue (MALT) lymphomas. This
results in cell accumulation as a consequence of prolonged cell
survival. In contrast, high-growth fraction lymphomas are characterized
by an enhanced proliferative activity, as a result of the deregulation
of oncogenes with cell cycle regulatory functions, such as
BCL6, in large B-cell lymphoma, or c-myc, in
Burkitt lymphoma. Low- and high-growth fraction lymphomas are both able
to accumulate other alterations in cell cycle regulation, most
frequently involving tumor suppressor genes such as
p16INK4a, p53, and
p27KIP1. As a consequence, these tumors behave
as highly aggressive lymphomas. The simultaneous inactivation of
several of these regulators confers increased aggressivity and
proliferative advantage to tumoral cells. In this review we discuss our
current knowledge of the alterations in each of these pathways, with
special emphasis on the deregulation of cell cycle progression, in an
attempt to integrate the available information within a global model
that describes the contribution of these molecular changes to the
genesis and progression of B-cell lymphomas.
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