Pharmacologic purging of malignant T cells from human bone marrow using 9-beta-D-arabinofuranosylguanine.
Arabinosylguanine (araG) is a nucleoside analog that is rapidly converted by cells of the T lymphoid lineage to its corresponding arabinosylguanine nucleotide triphosphate, resulting in inhibition of DNA synthesis and selective in vitro toxicity to T lymphoblastoid cell lines as well as to freshly isolated leukemia cells from patients with T cell acute lymphoblastic leukemia. In this report, we demonstrate that araG is an effective agent to use for chemoseparation of malignant T lymphoblasts from human bone marrow. When freshly isolated human T leukemia cells or T lymphoblastoid cells were treated with 100 microM araG for 18 hr, up to 6 logs of clonogenic T cells could be eliminated without appreciable toxicity to the normal myeloid, erythroid, and megakaryocytoid clonal progenitor cells. We discuss the use of this agent in ex vivo elimination of residual malignant T cells from marrow of patients requiring myeloablative chemotherapy with autologous bone marrow rescue.
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710.
M E
ME
Hebert
M L
ML
Greenberg
S
S
Chaffee
L
L
Gravatt
M S
MS
Hershfield
G B
GB
Elion
J
J
Kurtzberg
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001087:Arabinonucleosides / Q000009:adverse effects / Q000494:pharmacology*; D001088:Arabinonucleotides / Q000378:metabolism; D016465:Bone Marrow Purging; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002999:Clone Cells / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015649:Pentostatin / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D001088:Arabinonucleotides; C028771:9-arabinofuranosylguanine; D015649:Pentostatin; C022206:9-beta-D-arabinofuranosylguanosine 5'-triphosphate; D006160:Guanosine Triphosphate