Abstract
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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Antineoplastic Agents / adverse effects
-
Antineoplastic Agents / pharmacology*
-
Arabinonucleosides / adverse effects
-
Arabinonucleosides / pharmacology*
-
Arabinonucleotides / metabolism
-
Bone Marrow Purging*
-
Cell Death / drug effects
-
Cell Division / drug effects
-
Cell Separation
-
Clone Cells / drug effects
-
Erythroid Precursor Cells / cytology
-
Erythroid Precursor Cells / drug effects
-
Erythroid Precursor Cells / metabolism
-
Guanosine Triphosphate / analogs & derivatives
-
Guanosine Triphosphate / metabolism
-
Humans
-
Leukemia-Lymphoma, Adult T-Cell / drug therapy
-
Leukemia-Lymphoma, Adult T-Cell / metabolism
-
Leukemia-Lymphoma, Adult T-Cell / pathology
-
Pentostatin / pharmacology
-
Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
-
Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
-
T-Lymphocytes / drug effects*
-
T-Lymphocytes / metabolism
-
T-Lymphocytes / pathology
-
Tumor Cells, Cultured
Substances
-
Antineoplastic Agents
-
Arabinonucleosides
-
Arabinonucleotides
-
9-arabinofuranosylguanine
-
Pentostatin
-
9-beta-D-arabinofuranosylguanosine 5'-triphosphate
-
Guanosine Triphosphate