ISSN 1062-3604, Russian Journal of Developmental Biology, 2006, Vol. 37, No. 3, pp. 187–192. © Pleiades Publishing, Inc., 2006.
Original Russian Text © G.I. Abelev, 2006, published in Ontogenez, 2006, Vol. 37, No. 3, pp. 227–233.
Differentiation antigens in the normal and neoplas-
tic cells are markers of the level and direction of their
differentiation. In the hemopoietic cells, differentiation
antigens are presented by several families of surface
CD (cluster differentiation) antigens, while in the epi-
thelial cells, they are known as tissue speciﬁc antigens
including intracellular macromolecules and macromol-
ecules localized on the membrane. The fate of differen-
tiation antigens in the course of transformation and
tumor progression reﬂects the preservation, alteration,
or loss of differentiation by the cells subject to these
processes. From this viewpoint, differentiation antigens
behave oppositely in hemoblastoses and carcinomas:
hemoblastoses preserve in all details the level and
direction of differentiation of the progenitor cell, while
carcinomas lose their differentiation antigens step by
step including full dedifferentiation and often reexpress
embryonic differentiation antigens (Weiler, 1959;
Abelev, 1965; Ku et al., 1999).
We proposed that these differences in behavior of
the differentiation antigens in both systems are related
to different pathways of tumor progression in these sys-
tems (Abelev, 2000, 2003). We believe also that tumor
progression in hemoblastoses does not change the dif-
ferentiation status of a neoplastic cell, while carcino-
mas overcome the normalizing control of microenvi-
ronment and develop full or partial independence from
the factors of microenvironment, which, at the same
time, determine and maintain epithelial differentiation.
Relationship Between Differentiation
and Transformation and Progression in Hemoblastoses
The mechanisms of transformation in tumors of the
hemopoietic tissues are intimately related to the mech-
anisms of its differentiation (Abelev, 2000; Tenen,
2003). The oncogene activation in Burkitt’s lymphoma
is a classical example of such an intimate relationship.
In this tumor, oncogene
is translocated to the
genes of immunoglobulin I- or L-chains (IgH e IgL),
which are active in A-cells and control synthesis of
these polypeptide chains. Synthesis of IgH speciﬁc for
this class and parallel synthesis of IgL are a key event
in differentiation of A-cells. Translocation of MYC to
an enhancer of the immunoglobulin genes (
) leads to constitutive oncogene expression,
which is, thus inseparable from the differentiation sta-
tus of a progenitor cell of A-cellular tumor. Moreover,
the translocation per se occurs due to the mechanisms
of genetic recombination which are, at this stage of dif-
ferentiation, characteristic for B-cells during synthesis
of IgH or IgL chains (Klein,1982; Korsmeyer, 1992).
Similar mechanisms were described in some other
B-cellular lymphomas: follicular lymphoma when gene
is activated upon transfer to the enhancer of IgH-
chain gene and some lymphomas of germinal centers or
chronic lymphocytic leukemia (Korsmeyer, 1992).
Very close mechanisms of oncogene activation are
involved in acute T-cellular leucoses (T-ALL). Here,
OF TUMOR GROWTH
Differentiation Antigens of Hemoblastoses
and Epithelial Tumors: Relations
to the Mechanisms of Transformation and Progression
G. I. Abelev
Institute of Carcinogenesis, Blokhin Russian Cancer Research Center, Russian Academy
of Medical Sciences, Kashirskoe sh. 24, Moscow, 115478 Russia
Received October 10, 2005; in ﬁnal form, December 6, 2005
—The role of mechanisms underlying differentiation is considered in malignant transformation of
hemoblastoses and epithelial tumors. In hemoblastoses, differentiation is intimately related to malignant trans-
formation and they are underlain by the same mechanisms. Immunophenotyping of hemoblastoses is fully
based on successive stages of their differentiation with characteristic expression of differentiation antigens.
Unlike hemoblastoses, epithelial tumors gradually, in the course of progression, lose their differentiation due
to the degradation of the connections with the microenvironment, which controls the direction and level of epi-
thelial differentiation. Therefore, carcinomas are characterized by varying degrees of “antigenic simpliﬁca-
tion”, including the epithelial-mesenchymal transition.
: differentiation of hemoblastoses, differentiation of epithelial neoplasms; immunophenotyping of
hemoblastoses, antigenic simpliﬁcation of carcinomas, progression and differentiation of tumors, tumor mark-
ers, epithelial-mesenchymal transition, role of microenvironment in tumor progression.