Studies on Human Leukemia. I. Spontaneous Lymphoblastoid Transformation of Fibroblastic Bone Marrow Cultures Derived From Leukemic and Nonleukemic Children23

Abstract

Bone marrow cells from 33 leukemic and 68 nonleukemic children were propagated in long-term tissue culture. Fibroblastic monolayer cultures were obtained from 24 of 43 (56%) specimens taken from the leukemic children when in relapse, from 52 of 79 (66%) specimens taken from the leukemic children when in remission, and from 47 of 71 (66%) specimens from nonleukemic children. Of the 123 fibroblastic cultures obtained, 110 were carried in serial passages and observed for 100 to 300 days. Four fibroblastic cultures, 2 derived from 2 children with acute leukem ia in remission, a culture from a child with infectious mononucleosis, and a culture from a child with hemolytic anemia and thrombocytopenia, showed a spontaneous lymphoblastoid transformation. This usually occurred in secondary (P₁) cultures. The spontaneously transformed cultures con sisted of a mixture of fibroblastic and lymphoblastoid cells of various sizes. The latter cells actively multiplied, either free in the supernatant fluid or on the fibroblastic monolayer, forming three-dimensional clusters. Cytologically, the lymphoblastoid cells strongly resembled the immature cells seen in direct smear preparations from bone marrow aspirates of leukemic children during the acute stage of the disease. All transformed cultures were serially propagated for prolonged periods, and they maintained their altered appearance. The phenomenon of “emperipolesis” was observed in all transformed cultures. With the depletion of fibroblastic cells, usually between the 10th and 15th serial transfers, the lymphoblastoid cells ceased multiplying and the cultures degenerated.