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| Establishment and characterization of a novel acute promyelocytic leukemia cell line (UF-1) with retinoic acid-resistant features |
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| Author(s): Kizaki M, Matsushita H, Takayama N, Muto A, Ueno H, Awaya N, Kawai Y, Asou H, Kamada N, Ikeda Y |
| Source: BLOOD Volume: 88 Issue: 5 Pages: 1824-1833 Published: SEP 1 1996 |
| Times Cited: 59 References: 35 |
| Abstract: All-trans retinoic acid (RA) induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL). Nevertheless, most of these patients develop RA resistance and relapse. The mechanisms of RA resistance by APL cells are still unclear. To understand the characteristics of human leukemia, human leukemic cell lines are useful tools for study. APL cells have a strikingly low proliferation potential in vitro; thus, only one APL cell line has been established. We developed a novel APL cell line (UF-1) from a patient clinically resistant to all-trans RA. Cell surface markers in the UF-1 cells were positive for CD7, CD13, CD33, and CD38. Cytogenetic analyses revealed additional abnormalities, 46XX, add(1)(q44), add(6)(q12), add(7)(q36), t(15;17) (q21;q21). Molecular analyses showed a PML/RAR alpha fusion transcript, Sequence analysis of the RAR alpha gene in RA-resistant HL-60 cells disclosed a point mutation in codon 411 (C to T substitution), whereas UF-1 cells showed the normal sequence. All-trans RA did not change morphological features of the cell, NET reduction activity, or their expression of CD11b antigens as determined by FAGS analysis except at 10(-6) mol/L. RA also did not alter the growth curve of the cells as determined by the MTT assay. These findings suggest that the UF-1 cell is the first permanent cell line with spontaneous RA-resistant APL cells. This RA-resistant APL cell line may be a useful model for molecular studies on the block of leukemic cell differentiation and as a means to investigate the mechanisms of RA resistance. (C) 1996 by The American Society of Hematology. |
| Document Type: Article |
| Language: English |
| Reprint Address: Kizaki, M (reprint author), KEIO UNIV, SCH MED, DIV HEMATOL, SHINJUKU KU, 35 SHINANOMACHI, TOKYO 160, JAPAN |
Addresses:
1. KEIO UNIV, SCH MED, CLIN LABS, SHINJUKU KU, TOKYO 160, JAPAN
2. HIROSHIMA UNIV, NUCL MED & BIOL RES INST, DEPT HEMATOL, HIROSHIMA 734, JAPAN |
| Publisher: W B SAUNDERS CO, INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 |
| Subject Category: Hematology |
| IDS Number: VE234 |
| ISSN: 0006-4971 |
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