Most human
lymphomas remain heterogeneous
biologic entities in spite of recent advances in the description of their clinical presentation, cellular morphology, immunophenotype, and genotype. Elucidation of genetic alterations causing malignant transformation may explain pathogenesis, refine differential diagnosis, clarify prognosis, and provide rational basis for new
therapy. During the last year the expression of
anaplastic lymphoma kinase clarified presentation and provided clues toward the outcome of
anaplastic large cell lymphoma; the breakpoints of t(2;5) were mapped; constitutive activation of
anaplastic lymphoma kinase by a
chromosomal inversion was described; transformation was shown to be independent of nuclear localization of
anaplastic lymphoma kinase; and
phospholipase C-gamma was identified as a molecular target for the
kinase activity of
anaplastic lymphoma kinase. Molecular characterization of recurrent
chromosome abnormalities has identified new candidate oncogenes: bcl-9, bcl-10, PAX-5, MMSET, and c-maf. Their precise role in malignant transformation, and the frequency of their alteration in
lymphoma and myeloma, is not yet defined. The expression of the antiapoptotic
protein bcl-2 on aggressive
lymphomas was shown to be associated with inferior disease-free survival by several investigators. This may be a target of pharmacologic reduction of bcl-2 levels. Can these advances in molecular pathogenesis improve cure rates for
lymphoma? The spectacularly successful molecular modeling of inhibitors for
HIV protease suggests that this may be an attainable objective.