title: Myeloablative treatment supported by autologous stem cell infusion with neuroblastoma.
abstract: Bcr-abl antisense oligodeoxynucleotides (AS-ODNs) have provided evidence of an antileukemia effect when tested in vitro against Philadelphia-positive cells. In order to investigate the efficacy of AS-ODNs as purging agents in chronic myeloid leukemia (CML) patients, K562 cells, a human CML cell line, were treated in vitro with various types of AS-ODNs and interferon-alpha. Cells were treated in vitro for 0 and 36 hr with 40 microgram/mL of AS-ODNs, respectively, and incubated at 37 degrees C for 36 hr. Cytotoxic effects were measured by counting the number of viable cells as well as by MTT test. Clonogenic activities were evaluated by methylcellulose culture for 2 weeks. The effects of purging agents on the rearrangement of bcrabl gene were evaluated by RT-PCR. AS-ODNs inhibited the proliferation of K562 cells with time in cell count assay and MTT test. AS-ODNs were superior to INF-alpha in inhibiting clonogenic activity (recovery rate; 26.3% vs 64.0%). After incubation with bcr-abl AS-ODNs primers and mRNA isolated from K562 cells, positive bands were abolished, especially of b3a2 type and phosphorothioate type. Our results suggest that AS-ODNs mediated purging may be one of the efficient methods and that autograft may be an alternative treatment for allograft in high-risk group patients of CML if they do not have a stem cell donor.
authors.affiliation: Department of Pediatrics, Ewha Womans University College of Medicine, Seoul, Korea.
authors.forename: Kyung Ha
authors.initials: KH
authors.lastname: Ryu
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Seoh
authors.forename: Pil Sang
authors.initials: PS
authors.lastname: Jang
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Kim
authors.forename: Sang Hyeok
authors.initials: SH
authors.lastname: Koh
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Shin
authors.forename: Hyo Seop
authors.initials: HS
authors.lastname: Ahn
mesh_terms: D016465:Bone Marrow Purging; D003114:Colony-Forming Units Assay; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D009447:Neuroblastoma / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000378:metabolism* / Q000627:therapeutic use; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured
chemical_list: D016376:Oligonucleotides, Antisense; D016044:Fusion Proteins, bcr-abl