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Plasma cell myeloma--new biological insights and advances in therapy
B Barlogie, J Epstein, P Selvanayagam and R Alexanian
University of Texas M.D. Anderson Cancer Center, Department of Hematology,
Houston 77030.
Plasma cell myeloma is a more complex neoplasm than suggested by the
relative uniformity of its dominant plasma cells, which represent the
terminal stage of normal B-cell differentiation. Phenotypic, molecular, and
cellular genetic data favor the presence of a myeloma stem cell early in
hematopoietic development so that, as in chronic myelogenous leukemia
(CML), a far distance exists between the primordial malignant cell that was
the target of malignant transformation and the dominant clinical phenotype.
Traces of pre-B, myeloid, and T cells are coexpressed with the mature
B-cell phenotype, an occurrence unknown in normal B-cell differentiation.
Analogous to CML, disease progression is marked by disease
dedifferentiation, occasionally with cessation of myeloma protein
production and development instead of extramedullary lymphomalike features
with high LDH or myelodysplasia/acute myelogenous leukemia (AML) syndromes.
The prognostic importance of serum LDH levels even in newly diagnosed
myeloma suggests the early presence of tumor cells with "LDH phenotype,"
which, as a result of drug resistance and proliferative advantage, expand
preferentially during disease progression. Further characterization of
these cells may provide important clues about the ontogeny of multiple
myeloma. Myeloma cells express many receptors for different biological
signals that might be exploitable for therapy with immunotoxins or
radioisotopes. Plasma cells and their precursors also produce a variety of
cytokines, some of which have putatively autostimulatory functions (eg,
IL-1, IL-5, IL-6) and/or are related to disease manifestations (eg, IL-1
and TNF-beta as OAF). The wealth of cellular expression by plasma cells
provides clues for understanding the mechanisms of gene activation and the
nature of abnormal growth and differentiation. The accuracy of
prognostically relevant staging systems has been refined with the use of
new quantitative parameters that reflect tumor mass (ie, serum B2M levels)
and biology. Further studies of cellular and molecular biology (ie, CAL-
LA, H-ras) may reveal those tumor cell features that define clinical
entities, response to therapy, and long-term prognosis. The lack of a major
advance in prognosis despite the use of more drugs and more intensive
regimens justifies the continued use of standard melphalan- prednisone for
patients with a highly favorable prognosis, for the very aged, and for
those with a short life expectancy due to other major medical problems.
However, a radical departure from standard practice is required to improve
the prognosis for younger patients with poor risk features.(ABSTRACT
TRUNCATED AT 400 WORDS)
Volume 73,
Issue 4,
pp. 865-879,
03/01/1989
Copyright © 1989 by The American Society of Hematology
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