scholarly journals Comparative cellular pharmacology of daunorubicin and idarubicin in human multidrug-resistant leukemia cells

Blood ◽  
1992 ◽  
Vol 79 (12) ◽  
pp. 3267-3273 ◽  
Author(s):  
E Berman ◽  
M McBride
Keyword(s):  
Growth Inhibition ◽  
Cell Line ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Fold Increase ◽  
Multidrug Resistant ◽  
Fresh Medium ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Cellular Pharmacology

Abstract We examined the effect of daunorubicin (DNR), the new anthracycline derivative idarubicin (IDR), and verapamil on two leukemia cell lines that displayed the multidrug resistant (MDR) phenotype and used laser flow cytometry to quantitate intracellular anthracycline content. The vinblastine-resistant human lymphoblastic leukemia cell line CEM-VBL demonstrated minimal DNR uptake; simultaneous incubation with verapamil and DNR increased intracellular DNR uptake fourfold. IDR uptake was 10 times more rapid in these cells and simultaneous incubation with IDR and verapamil resulted in only a 1.2-fold increase of intracellular IDR. Similar results were observed in the vincristine-resistant human myeloid leukemia cell line HL-60/RV+. Intracellular retention of DNR and IDR was also measured in each cell line. In CEM-BVL cells, 38% of the original DNR concentration remained after a 2-hour resuspension in fresh medium compared with 71% of the original IDR concentration. In HL- 60/RV+ cells, 36% of the DNR concentration remained compared with 51% of the IDR concentration. After incubation of CEM-VBL and HL-60/RV+ cells with DNR for 1 hour followed by resuspension in fresh medium plus verapamil, intracellular DNA retention increased 5- and 5.2-fold, respectively. However, incubation of these cells for 1 hour with IDR followed by resuspension in fresh medium plus verapamil resulted in only a 1.6- and 2.4-fold increase in intracellular IDR retention. Lastly, clonogenic experiments were performed to correlate intracellular anthracycline content with cytotoxicity. DNR alone had a minimal effect on the clonogenic growth of CEM-VBL cells, whereas the combination of DNR plus verapamil resulted in approximately 80% growth inhibition. However, incubation of these cells with IDR alone resulted in greater than 95% growth inhibition. These results suggest that IDR may be more effective than DNR in leukemia cells that display the MDR phenotype.

scholarly journals Comparative cellular pharmacology of daunorubicin and idarubicin in human multidrug-resistant leukemia cells

Blood ◽  
1992 ◽  
Vol 79 (12) ◽  
pp. 3267-3273 ◽  
Author(s):  
E Berman ◽  
M McBride
Keyword(s):  
Growth Inhibition ◽  
Cell Line ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Fold Increase ◽  
Multidrug Resistant ◽  
Fresh Medium ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Cellular Pharmacology

We examined the effect of daunorubicin (DNR), the new anthracycline derivative idarubicin (IDR), and verapamil on two leukemia cell lines that displayed the multidrug resistant (MDR) phenotype and used laser flow cytometry to quantitate intracellular anthracycline content. The vinblastine-resistant human lymphoblastic leukemia cell line CEM-VBL demonstrated minimal DNR uptake; simultaneous incubation with verapamil and DNR increased intracellular DNR uptake fourfold. IDR uptake was 10 times more rapid in these cells and simultaneous incubation with IDR and verapamil resulted in only a 1.2-fold increase of intracellular IDR. Similar results were observed in the vincristine-resistant human myeloid leukemia cell line HL-60/RV+. Intracellular retention of DNR and IDR was also measured in each cell line. In CEM-BVL cells, 38% of the original DNR concentration remained after a 2-hour resuspension in fresh medium compared with 71% of the original IDR concentration. In HL- 60/RV+ cells, 36% of the DNR concentration remained compared with 51% of the IDR concentration. After incubation of CEM-VBL and HL-60/RV+ cells with DNR for 1 hour followed by resuspension in fresh medium plus verapamil, intracellular DNA retention increased 5- and 5.2-fold, respectively. However, incubation of these cells for 1 hour with IDR followed by resuspension in fresh medium plus verapamil resulted in only a 1.6- and 2.4-fold increase in intracellular IDR retention. Lastly, clonogenic experiments were performed to correlate intracellular anthracycline content with cytotoxicity. DNR alone had a minimal effect on the clonogenic growth of CEM-VBL cells, whereas the combination of DNR plus verapamil resulted in approximately 80% growth inhibition. However, incubation of these cells with IDR alone resulted in greater than 95% growth inhibition. These results suggest that IDR may be more effective than DNR in leukemia cells that display the MDR phenotype.

Establishment of a NOD/SCID/γc−/−-Dependent Lymphoid Leukemia Cell Line, D593, with Novel RUNX1-LAF4 Fusion Gene.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4276-4276
Author(s):  
Akihiro Abe ◽  
Manabu Ninomiya ◽  
Shizuka Imagama ◽  
Momoko Suzuki ◽  
Fumihiko Hayakawa ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Cell Receptor ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Pcr Analysis ◽  
Lymphoid Leukemia

Abstract We established a NOD/SCID/γc−/−(NOG mouse)-dependent human lymphoid leukemia cell line, D593, by repeated xenotransplantation of pediatric T-cell acute lymphoblastic leukemia cells with the translocation t(2;21). The cell line, D-593, could be serially transplanted from mouse to mouse over a 2-year period. D593 had the same immuno-phenotype as the original leukemia cells: positive for CD2, 5, 7, 14, and 34, and negative for CD3, 4, 8, 19, and 41a. Cytoplasmic CD3 was positive and the rearrangement of T-cell receptor was detected by Southern blot analysis. A previously unreported translocation of t(2;21)(q11;q22) was observed in both the original patient sample and D593. The split signal of RUNX1 was detected by fluorescence in site hybridization in D593 indicating the involvement of RUNX1. Using 3′-RACE and RT-PCR analysis, we identified novel chimeric transcripts of RUNX1-LAF4 joining exon 7 of RUNX1 to exon 4 of LAF4. In the transplanted NOG mice, D593 homed into the trabecular endosteal region of bone marrow (BM), and proliferated from the endosteum to medulla. At the late stage of engraftment, the BM was filled with human lymphoblasts and metastases into the trabecular of the spleen and Glisson’s sheath of the liver were also observed. These findings suggest that D593 is a useful cell line to study not only the leukemia-related biology of RUNX1-LAF4 but also the novel therapeutic model against core-binding factor (CBF) leukemia.

scholarly journals Human acute leukemia cell line with the t(4;11) chromosomal rearrangement exhibits B lineage and monocytic characteristics

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 21-31 ◽  
Author(s):  
RC Stong ◽  
SJ Korsmeyer ◽  
JL Parkin ◽  
DC Arthur ◽  
JH Kersey
Keyword(s):  
Acute Leukemia ◽  
Cell Line ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Leukemic Cells ◽  
Leukemia Cell Line ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Immunoglobulin Gene ◽  
A Cell ◽  
B Lineage

Abstract A cell line, designated RS4;11, was established from the bone marrow of a patient in relapse with an acute leukemia that was characterized by the t(4;11) chromosomal abnormality. The cell line and the patient's fresh leukemic cells both had the t(4;11)(q21;q23) and an isochromosome for the long arm of No. 7. Morphologically, all cells were lymphoid in appearance. Ultrastructurally and cytochemically, approximately 30% of the cells possessed myeloid features. The cells were strongly positive for terminal deoxynucleotidyl transferase. They were HLA-DR positive and expressed surface antigens characteristic for B lineage cells, including those detected by anti-B4, BA-1, BA-2, and PI153/3. Immunoglobulin gene analysis revealed rearrangements of the heavy chain and kappa chain genes. The cells lacked the common acute lymphoblastic leukemia antigen and antigenic markers characteristic of T lineage cells. The cells reacted with the myeloid antibody 1G10 but not with other myeloid monoclonal antibodies. Treatment with 12-O-tetradecanoyl- phorbol-13-acetate induced a monocyte-like phenotype demonstrated by cytochemical, functional, immunologic, and electron microscopic studies. The expression of markers of both early lymphoid and early myeloid cells represents an unusual phenotype and suggests that RS4;11 represents a cell with dual lineage capabilities. To our knowledge, RS4;11 is the first cell line established from t(4;11)-associated acute leukemia.

Activation ofHOX11L2 by juxtaposition with 3?-BCL11B in an acute lymphoblastic leukemia cell line (HPB-ALL) with t(5;14)(q35;q32.2)

2003 ◽  
Vol 37 (1) ◽  
pp. 84-91 ◽  
Author(s):  
Roderick A.F. MacLeod ◽  
Stefan Nagel ◽  
Maren Kaufmann ◽  
Johannes W.G. Janssen ◽  
Hans G. Drexler
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cell Line ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Lymphoblastic Leukemia Cell Line

scholarly journals The oxidation of (−)-epigallocatechin-3-gallate inhibits T-cell acute lymphoblastic leukemia cell line HPB-ALL via the regulation of Notch1 expression

RSC Advances ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 1679-1684 ◽  
Author(s):  
Yu-Na Wang ◽  
Jing Wang ◽  
Hao-Nan Yang ◽  
Bang-Lei Zhang ◽  
Pan Zhang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cell Line ◽  
Hematological Malignancy ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Activating Mutations ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia Cell Line

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy, and commonly associated with activating mutations in the Notch1 pathway.

scholarly journals Dye-mediated photolysis is capable of eliminating drug-resistant (MDR+) tumor cells

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 793-800 ◽  
Author(s):  
RM Lemoli ◽  
T Igarashi ◽  
M Knizewski ◽  
L Acaba ◽  
A Richter ◽  
...  
Keyword(s):  
Cell Line ◽  
Tumor Cells ◽  
Cell Lines ◽  
Light Exposure ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line ◽  
Drug Resistant ◽  
Colony Forming Unit

Abstract We evaluated the potential role of photoradiation therapy with a benzoporphyrin derivative, monoacid ring A (BPD-MA), and dihematoporphyrin ether (DHE), for the ex vivo purging of residual tumor cells from autologous bone marrow (BM) grafts. BPD-MA and DHE photosensitizing activity was tested against two human large-cell lymphoma cell lines and colony-forming unit-leukemia (CFU-L) derived from patients with acute myelogenous leukemia (AML). In mixing experiments, 4-log elimination of tumor cell lines was observed after 1 hour of incubation with 75 ng/mL of BPD-MA or 30 minutes of treatment with 12.5 micrograms/mL of DHE followed by white light exposure. By comparison, using the same concentration of BPD-MA, the mean recovery of normal BM progenitors was 4% +/- 0.8% (mean +/- SD) for granulocyte- macrophage colony-forming unit (CFU-GM) and 5% +/- 0.8% for burst- forming unit-erythroid (BFU-E). Similarly, DHE treatment resulted in the recovery of 5.2% +/- 2% and 9.8% +/- 3% of CFU-GM and BFU-E, respectively. Furthermore, equivalently cytotoxic concentrations of both DHE and BPD-MA and light were found not to kill normal pluripotent stem cells in BM, as demonstrated by their survival in two-step long- term marrow culture at levels equal to untreated controls. The T- lymphoblastic leukemia cell line CEM and its vinblastine (VBL)- resistant subline CEM/VBL, along with the acute promyelocyte leukemia cell line HL-60 and its vincristine (VCR)-resistant subline HL-60/VCR, were also tested. BPD-MA at 75 ng/mL was able to provide a greater than 4-log elimination of the drug-sensitive cell lines, but only a 34% and 55% decrease of the drug-resistant HL-60/VCR and CEM/VBL cell lines, respectively. On the contrary, 12.5 micrograms/mL of DHE reduced the clonogenic growth of all the cell lines by more than 4 logs. Further experiments demonstrated decreased uptake of both BPD-MA and DHE by the resistant cell lines. However, all the cell lines took up more DHE than BPD-MA under similar experimental conditions. Our results demonstrate the preferential cytotoxicity of BPD-MA and DHE toward neoplastic cell lines and CFU-L from AML patients. In addition, DHE was slightly more effective in purging tumor cells expressing the p-170 glycoprotein. These results suggest that photoradiation with DHE would be useful for in vitro purging of residual drug-resistant leukemia and lymphoma cells.

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