Abstract
AP-1060 is a newly established acute promyelocytic leukemia (APL) cell line from a multiple-relapse patient clinically resistant to both all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). The line was initially derived as a granulocyte colony-stimulating factor-dependent strain that underwent replicative senescence and, following ethylnitrosourea treatment, as a phenotypically similar immortalized line. Immortalization was associated with broadened cytokine sensitivity but not growth autonomy, in contrast to three previously derived APL lines. Both the AP-1060 strain and line had shortened telomeres and low telomerase activity, while the line had higher expression of many genes associated with macromolecular synthesis. The karyotype was 46,XY,t(3;14)(p21.1;q11.2),t(15;17)(q22;q11) [100%]; the unique t(3;14) was observed in 4/9 t(15;17)-positive metaphase cells at previous relapse on ATRA therapy. The PML-RARα mRNA harbored a missense mutation in the RARα-region ligand-binding domain (Pro900Ser). This was associated with a right-shift and sharpening of the ATRA-induced maturation response compared to ATRA-sensitive NB4 cells, which corresponded to the transcriptional activation by PML-RARαω Prog900Ser of a cotransfected ATRA-targeted reporter vector in COS-1 cells. AP-1060 also manifested relative resistance to ATO-induced apoptosis at ≥ 1 μM, while 0.25 μM ATO stimulated limited atypical maturation. These findings suggest that AP-1060 will be useful for further assessing molecular elements involved in APL progression and drug response/resistance.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1258-1269 |
| Number of pages | 12 |
| Journal | Leukemia |
| Volume | 18 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2004 |
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Keywords
- Acute promyelocytic leukemia
- Arsenic trioxide resistance
- Cell strain immortalization
- Cytokine-dependent cell line
- Retinoic acid resistance
ASJC Scopus subject areas
- Hematology
- Cancer Research
Cite this
Acute promyelocytic leukemia cell line AP-1060 established as a cytokine-dependent culture from a patient clinically resistant to all-trans retinoic acid and arsenic trioxide. / Sun, Y.; Kim, S. H.; Zhou, D. C.; Ding, W.; Paietta, Elisabeth M.; Guidez, F.; Zelent, A.; Ramesh, K.h.; Cannizzaro, L.; Warrell, R. P.; Gallagher, R. E.
In: Leukemia, Vol. 18, No. 7, 07.2004, p. 1258-1269.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Acute promyelocytic leukemia cell line AP-1060 established as a cytokine-dependent culture from a patient clinically resistant to all-trans retinoic acid and arsenic trioxide
AU - Sun, Y.
AU - Kim, S. H.
AU - Zhou, D. C.
AU - Ding, W.
AU - Paietta, Elisabeth M.
AU - Guidez, F.
AU - Zelent, A.
AU - Ramesh, K.h.
AU - Cannizzaro, L.
AU - Warrell, R. P.
AU - Gallagher, R. E.
PY - 2004/7
Y1 - 2004/7
N2 - AP-1060 is a newly established acute promyelocytic leukemia (APL) cell line from a multiple-relapse patient clinically resistant to both all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). The line was initially derived as a granulocyte colony-stimulating factor-dependent strain that underwent replicative senescence and, following ethylnitrosourea treatment, as a phenotypically similar immortalized line. Immortalization was associated with broadened cytokine sensitivity but not growth autonomy, in contrast to three previously derived APL lines. Both the AP-1060 strain and line had shortened telomeres and low telomerase activity, while the line had higher expression of many genes associated with macromolecular synthesis. The karyotype was 46,XY,t(3;14)(p21.1;q11.2),t(15;17)(q22;q11) [100%]; the unique t(3;14) was observed in 4/9 t(15;17)-positive metaphase cells at previous relapse on ATRA therapy. The PML-RARα mRNA harbored a missense mutation in the RARα-region ligand-binding domain (Pro900Ser). This was associated with a right-shift and sharpening of the ATRA-induced maturation response compared to ATRA-sensitive NB4 cells, which corresponded to the transcriptional activation by PML-RARαω Prog900Ser of a cotransfected ATRA-targeted reporter vector in COS-1 cells. AP-1060 also manifested relative resistance to ATO-induced apoptosis at ≥ 1 μM, while 0.25 μM ATO stimulated limited atypical maturation. These findings suggest that AP-1060 will be useful for further assessing molecular elements involved in APL progression and drug response/resistance.
AB - AP-1060 is a newly established acute promyelocytic leukemia (APL) cell line from a multiple-relapse patient clinically resistant to both all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). The line was initially derived as a granulocyte colony-stimulating factor-dependent strain that underwent replicative senescence and, following ethylnitrosourea treatment, as a phenotypically similar immortalized line. Immortalization was associated with broadened cytokine sensitivity but not growth autonomy, in contrast to three previously derived APL lines. Both the AP-1060 strain and line had shortened telomeres and low telomerase activity, while the line had higher expression of many genes associated with macromolecular synthesis. The karyotype was 46,XY,t(3;14)(p21.1;q11.2),t(15;17)(q22;q11) [100%]; the unique t(3;14) was observed in 4/9 t(15;17)-positive metaphase cells at previous relapse on ATRA therapy. The PML-RARα mRNA harbored a missense mutation in the RARα-region ligand-binding domain (Pro900Ser). This was associated with a right-shift and sharpening of the ATRA-induced maturation response compared to ATRA-sensitive NB4 cells, which corresponded to the transcriptional activation by PML-RARαω Prog900Ser of a cotransfected ATRA-targeted reporter vector in COS-1 cells. AP-1060 also manifested relative resistance to ATO-induced apoptosis at ≥ 1 μM, while 0.25 μM ATO stimulated limited atypical maturation. These findings suggest that AP-1060 will be useful for further assessing molecular elements involved in APL progression and drug response/resistance.
KW - Acute promyelocytic leukemia
KW - Arsenic trioxide resistance
KW - Cell strain immortalization
KW - Cytokine-dependent cell line
KW - Retinoic acid resistance
UR - http://www.scopus.com/inward/record.url?scp=3142667730&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3142667730&partnerID=8YFLogxK
U2 - 10.1038/sj.leu.2403372
DO - 10.1038/sj.leu.2403372
M3 - Article
VL - 18
SP - 1258
EP - 1269
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 7
ER -