Myeloablative treatment supported by autologous stem cell infusion with neuroblastoma.
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.
Ryu
Kyung Ha
KH
Department of Pediatrics, Ewha Womans University College of Medicine, Seoul, Korea.
Seoh
Ju Young
JY
Jang
Pil Sang
PS
Kim
Chul Woo
CW
Koh
Sang Hyeok
SH
Shin
Hee Young
HY
Ahn
Hyo Seop
HS
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
D016376:Oligonucleotides, Antisense; D016044:Fusion Proteins, bcr-abl