Myeloablative Treatment Supported by Autologous Stem Cell Infusion with Neuroblastoma.
10.3346/jkms.2003.18.2.184
- Author:
Kyung Ha RYU
1
;
Ju Young SEOH
;
Pil Sang JANG
;
Chul Woo KIM
;
Sang Hyeok KOH
;
Hee Young SHIN
;
Hyo Seop AHN
Author Information
1. Department of Pediatrics, Ewha Womans University College of Medicine, Seoul, Korea. hsahn@snu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Oligonucleotides, Antisense;
Leukemia, Myeloid, Chronic;
Philadephia Chromosome
- MeSH:
Bone Marrow Purging*;
Colony-Forming Units Assay;
Fusion Proteins, bcr-abl/genetics;
Fusion Proteins, bcr-abl/metabolism;
Hematopoietic Stem Cells/physiology*;
Human;
Leukemia, Myeloid, Chronic/therapy;
Neuroblastoma/therapy*;
Oligonucleotides, Antisense/metabolism*;
Oligonucleotides, Antisense/therapeutic use;
Transplantation, Autologous*;
Tumor Cells, Cultured
- From:Journal of Korean Medical Science
2003;18(2):184-190
- CountryRepublic of Korea
- Language:English
-
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.
