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 lineage 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 provided an objective marker of the neoplastic cell population. Relative amounts of clonally rearranged and germline antigen receptor gene DNA were assessed by Southern analysis of bone marrow cell DNA, before and after LTMC in studies on ten cases of non-Hodgkin's lymphoma (NHL), four of myeloma (MM), and two of chronic lymphocytic leukemia (CLL). Clonally rearranged DNA became undetectable during LTMC in 12 studies (seven NHL, four MM, one CLL), and in seven of these studies the extent of the decrease determined by densitometric analysis of rearranged and germline bands on the autoradiograms was sufficient to demonstrate that preferential loss of neoplastic relative to other cell series had taken place. At the same time, there was a net increase in normal myeloid series, to indicate that a selective adverse effect similar to that reported to operate on leukemic cells in LTMC also applied to certain malignancies involving the lymphocytic lineage. In four of the 16 studies (three NHL, one CLL), the neoplastic cells possessing clonally rearranged DNA were maintained in LTMC, demonstrating that susceptibility to this selective adverse effect was not a uniform characteristic of neoplastic lymphocytic disorders.