The association of nuclear blebs with aneuploidy in human acute leukemia.

lymphoma. Anderson (3) and McDuffie (1 2) independently observed similar structures in the bone marrow of untreated leukemic patients. In addition to these reports of inherent alterations due to a disease process, several investigators have shown that a group of DNA-inhibiting chemotherapeutic agents can also induce the formation of nuclear blebs. Stalzer et a!. (17), for instance, described the appearance of these alterations in bone marrow cells following 5-fluorouracil treatment in patients with neoplastic disease. Nuclear bleb formation in human bone marrow cells following administra tion of exceptionally high doses of cytosine arabinoside was initially reported by our laboratory in 1967 (2). We also demonstrated that the addition of this drug to short-term in vitro cultures of bone marrow cells leads to the appearance of similar nuclear changes. Further investigation of this phenomenon in the bone marrow of leukemic patients revealed that the blebs appeared more frequently in those specimens exhibiting chromosomal abnormalities. The incidence of these chromosomal alterations in the hematopoietic tissue from acute leukemic patients seen at this Institution was found to be approximately 41% (19). The present study was designed to investigate further the apparent association between aneuploidy and nuclear blebs in the bone marrow cells obtained from these leukemic patients.