MULTISTEP TRANSFORMATION IN LOW-GRADE LYMPHOPROLIFERATIVE DISEASES

Background: Carcinogenesis, the formation of solid tumors, is now wide ly accepted to represent a multistep process. Several genetic events, activation of proto-oncogenes and inactivation of tumor suppressor gen es, are involved. Design: Review of the literature for evidence that t he concept of multistep transformation has relevance also for the form ation of low-grade lymphoproliferative diseases. Results and conclusio n: The common translocations in low-grade lymphoid tumors are probably early events, predominantly involved in the activation of oncogenes, leading to growth stimulation or prolonged cell survival. As a result 'monoclonal lymphoproliferative disorders of undetermined significance (MLDUS)' occur, undetermined, because some translocations may not alw ays lead to tumor formation. For progression to full malignancy, addit ional genetic events are required besides sequential selection of vari ant subpopulations within the neoplastic clone. Recent data indicate t hat mutations and deletions of putative tumor suppressor genes, includ ing the P53 and retinoblastoma genes, are also involved in the progres sion of lymphoproliferative disorders. A list of lymphoproliferative d iseases stressing this concept of multistep transformation is presente d in this article.