ISSN 10227954, Russian Journal of Genetics, 2011, Vol. 47, No. 6, pp. 662–673. © Pleiades Publishing, Inc., 2011.
Original Russian Text © E.S. Zakharova, N.A. Kazilo, D.N. Stefanov, M.N. Sinitsyna, A.M. Kovrigina, 2011, published in Genetika, 2011, Vol. 47, No. 6, pp. 752–764.
Lymphomas are tumors originating from lymphoid
cells of the immune system that are divided into the B
and Tcell types. There is another type of tumors origi
nating from natural killer cells (NK cells). Comparison of
clinical, morphological, immunological, and genetic
characteristics of tumors of the hematopoietic and lym
phoid tissues revealed numerous nosological forms of B
and Tcell lymphomas requiring individual therapeutic
tactics and including numerous variants differing in the
clinical picture, morphological substrate, immunophe
notype, and genetic features . Most (85–95%) lym
phomas are of the Bcell type [2, 3]. According to the
data of 2008, the incidence of newly diagnosed diseases
of the lymphoid and hematopoietic tissues in Russia was
16.65 cases per 100000 individuals with a mean annual
increase of 2.3% .
Successful treatment of the disease and prognosis
of its progress depend on the identification of the
nosological form of lymphoma and its variant. Exact
and timely diagnostics is particularly important in
connection with the appearance of new therapeutic
preparations aimed at certain targets in a tumor cell.
Such a medicine in the case of Bcell lymphomas is
MabThera F. HoffmannLa Roche (Switzerland).
The active substance of this preparation represents a
chimeric antibody specifically recognizing the Blym
phocyte molecule, CD20. Introduction of the immu
nochemotherapeutic methods of treatment with the
use of MabThera permitted the cases of complete
remissions in some forms of Bcell lymphomas to be
increased up to more than 90% .
One of the primary tasks in diagnostics of B and
Tcell lymphomas at present is the use and propaga
tion of the molecular genetic methods of diagnosis
verification (method of clonality detection in a lym
phocyte population, in particular).
BCELL DIFFERENTIATION, ORIGIN
AND DIVERSITY OF LYMPHOMAS
In the course of development, lymphoid cells are
transformed from stem to mature cells and possess
properties determining individual stages of differentia
tion of Blymphocytes. Malignant transformation
characterized by “breakdowns” in the cell genetic
apparatus may occur at any stage of lymphocyte matu
ration, and thus the process of further differentiation
will be disturbed. The cell that gives birth to a tumor
pool will be a carrier of information on the molecular
and biological processes occurring in it at the moment
of genetic damage, and these processes will make their
contribution to the development and progress of the
Most stages of differentiation of Blymphocytes are
detected with the use of immunohistochemical markers.
Differentiation of Blymphocytes is divided into two
stages: antigenindependent and antigendependent
(Fig. 1). The first stage begins with the formation of a
hematopoietic stem cell in bone marrow. The following
step of cell differentiatiion in bone marrow are precur
sor cells (proBcells). Rearrangements of genes of the
heavy chains of immunoglobulins start at this level.
Then follows a preB cell (early and late stages are
distinguished). The rearrangements of the heavy
chains of immunoglobulins are completed after the
formation of a late preB cell. The next step is an
immature B cell. It is characterized by already rear
Genetic Bases of the Repertoire of Immunoglobulins
in Application to Diagnostics of Clonality of BCell
E. S. Zakharova
, N. A. Kazilo
, D. N. Stefanov
, M. N. Sinitsyna
, and A. M. Kovrigina
Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia
Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115578 Russia
Received September 21, 2010
—Molecular mechanisms underlying the formation of Bcell lymphomas in connection with pro
cesses associated with the maturation of Blymphocytes are reviewed. The currently used diagnostic methods
do not always distinguish lymphomas from reactive changes of the lymphoid tissue. The principle of the
molecular genetic method of clonality detection in lymphocyte populations, technical problems, and the
strategy of its application in clinical diagnostics of lymphomas are described in detail.