CLONALLY REARRANGED ANTIGEN RECEPTOR GENE DNA STUDIES IN EVALUATION OF SUSCEPTIBILITY OF NEOPLASTIC LYMPHOCYTIC AND PLASMACYTIC DISORDERS TO SELECTIVE LOSS IN LONG-TERM MARROW CULTURE

Survival of neoplastic cells of disorders involving the lymphocytic li neage in relation to normal hemopoietic cells has been investigated in long-term culture of bone marrow (LTMC) infiltrated by conditions in which a clonally rearranged B- or T-cell antigen receptor gene provide d an objective marker of the neoplastic cell population. Relative amou nts of clonally rearranged and germline antigen receptor gene DNA were assessed by Southern analysis of bone marrow cell DNA, before and aft er LTMC in studies on ten cases of non-Hodgkin's lymphoma (NHL), four of myeloma (MM), and two of chronic lymphocytic leukemia (CLL). Clonal ly rearranged DNA became undetectable during LTMC in 12 studies (seven NHL, four MM, one CLL), and in seven of these studies the extent of t he decrease determined by densitometric analysis of rearranged and ger mline bands on the autoradiograms was sufficient to demonstrate that p referential loss of neoplastic relative to other cell series had taken place. At the same time, there was a net increase in normal myeloid s eries, to indicate that a selective adverse effect similar to that rep orted to operate on leukemic cells in LTMC also applied to certain mal ignancies involving the lymphocytic lineage. In four of the 16 studies (three NHL, one CLL), the neoplastic cells possessing clonally rearra nged DNA were maintained in LTMC, demonstrating that susceptibility to this selective adverse effect was not a uniform characteristic of neo plastic lymphocytic disorders.