Pharmacologic marrow purging in murine T cell leukemia.
Deoxycoformycin in combination with deoxyadenosine was used to purge 6C3HED malignant T cells from murine marrow in vitro. Adenosine deaminase activity of 6C3HED cells was ablated by incubation with 10(-6) mol/L deoxycoformycin (dCF). During a 12-hour incubation with 10(-6) mol/L dCF and 10(-4) mol/L deoxyadenosine, tumor cells sequentially accumulated dATP, became depleted of NAD followed by ATP, then died. More than 5 logs of 6C3HED cells were killed as measured by survival of mice injected with treated tumor cells. Identical incubation of 5 x 10(6) marrow cells did not interfere with rescue of syngeneic lethally irradiated mice. Long-term survival was demonstrated in 12 of 14 mice that received marrow that had been contaminated with 5% 6C3HED cells, incubated with deoxycoformycin and deoxyadenosine, then used to rescue lethally irradiated mice. This murine model provides information not available from in vitro assays and may be useful in the development of strategies to purge malignant T cells from marrow.
Copelan
E A
EA
Ohio State University, Bone Marrow Transplantation Program, Columbus 43210.
Johnson
S C
SC
Grever
M R
MR
Sheridan
J F
JF
Tutschka
P J
PJ
D015720:5'-Nucleotidase; D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D003070:Coformycin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003839:Deoxyadenosines / Q000008:administration & dosage; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000187:drug effects; D009708:Nucleotidases / Q000378:metabolism; D015649:Pentostatin; D013601:T-Lymphocytes / Q000187:drug effects*
D003839:Deoxyadenosines; D003070:Coformycin; D015649:Pentostatin; D009708:Nucleotidases; D015720:5'-Nucleotidase; D000243:Adenosine Deaminase