Evidence for extensive intermolecular disulfide bonds of the proteins of non-ionic detergent high-salt-resistant skeletons of normal lymphocytes, and the altered structure in leukemia.

Normal and leukemic lymphocytes were subjected to lysis with a non-ionic detergent and 2.0 M NaCl. The intact nuclear DNA and the associated molecules resulting from these lyses (the nucleoids) were then separated from DNA-dissociated molecules and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Most of the proteins undissociable by 2.0 M NaCl from normal lymphocyte nuclear DNA or from DNA-associated molecules appear to be intermolecularly S-S linked. A distinct set of these proteins was either absent or only present in greatly decreased amounts in association with the leukemic lymphocyte nuclear DNA exposed to 2.0 M NaCl. On the other hand, the opposite relationship was found for a an MW 71,000 protein with leukemic lymphocytes of every patient studied regardless of the subtype of leukemia. Conversion of normal quiescent lymphocytes to cycling cells by lectin stimulation rendered them similar to leukemic cells in some respects but not in all. Our results show an altered nuclo(cyto)skeletal structure in leukemic cells; in general the proteins involved appear to be sulfhydryl proteins whose redox states and/or DNA association properties are modified by the neoplastic transformation of lymphocytes.