Open Access

In vivo, ex vivo and in vitro dasatinib activity in chronic lymphocytic leukemia

  • Authors:
    • Krzysztof Giannopoulos
    • Agnieszka Karczmarczyk
    • Marta Karp
    • Agnieszka Bojarska‑Junak
    • Kamila Kosior
    • Małgorzata Kowal
    • Waldemar Tomczak
    • Marek Hus
    • Marcin Machnicki
    • Tomasz Stokłosa
  • View Affiliations

  • Published online on: February 12, 2021     https://doi.org/10.3892/ol.2021.12546
  • Article Number: 285
  • Copyright: © Giannopoulos et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Dasatinib inhibits the breakpoint cluster region‑Abelson murine leukemia 1 (BCR‑ABL1) gene along with other kinases known to be overexpressed and abnormally active in patients with chronic lymphocytic leukemia (CLL). The current study used primary leukemic cells obtained from 53 patients with CLL that were treated with dasatinib. A 2,3‑bis‑(2‑methoxy‑4‑nitro‑5‑sulfophenyl)‑2H‑tetrazolium‑5‑carboxanilide (XTT) assay and Annexin V staining was performed to assess the cytotoxic effects of dasatinib treatment. The XTT assay revealed that the median cytotoxicity of dasatinib was 8.30% (range, 0.00‑77.89%). Due to high dispersion of dasatinib activity, patients were divided into sensitive (n=27; 50.94%; median cytotoxicity, 22.81%) and resistant groups (n=26; 49.06%; median cytotoxicity, 0.00%). A median cytotoxicity of 8.30% was selected as a cut off value. Using Annexin V staining and flow cytometry on exemplary sensitive and resistant CLL samples, it was revealed that 17.71 and 1.84% of cells were apoptotic, respectively. The current study presented a case of a patient with concomitant occurrence of CLL and chronic myeloid leukemia (CML) with a major molecular response after dasatinib treatment. A simultaneous reduction of circulating CLL cells indicated in vivo anti‑CLL activity induced by dasatinib. After an in vitro culture of the patient's mononuclear cells with subsequent dasatinib treatment, a higher percentage of CLL cells undergoing apoptosis was obsevered when compared with untreated samples (38.19 vs. 21.99%, respectively). Similarly, the percentage of CLL apoptotic cells (ΔΨmlow) measured by chloromethyl‑X‑rosamine was higher after incubation with dasatinib (7.28%) than in the negative control (2.86%). In conclusion, dasatinib induced antileukemic effects against CML and CLL cells. The results of the current study indicated that dasatinib may induce apoptosis ex vivo, in vitro and in vivo in CLL.
View Figures
View References

Related Articles

Journal Cover

April-2021
Volume 21 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Giannopoulos K, Karczmarczyk A, Karp M, Bojarska‑Junak A, Kosior K, Kowal M, Tomczak W, Hus M, Machnicki M, Stokłosa T, Stokłosa T, et al: In vivo, <em>ex vivo</em> and <em>in vitro</em> dasatinib activity in chronic lymphocytic leukemia. Oncol Lett 21: 285, 2021.
APA
Giannopoulos, K., Karczmarczyk, A., Karp, M., Bojarska‑Junak, A., Kosior, K., Kowal, M. ... Stokłosa, T. (2021). In vivo, <em>ex vivo</em> and <em>in vitro</em> dasatinib activity in chronic lymphocytic leukemia. Oncology Letters, 21, 285. https://doi.org/10.3892/ol.2021.12546
MLA
Giannopoulos, K., Karczmarczyk, A., Karp, M., Bojarska‑Junak, A., Kosior, K., Kowal, M., Tomczak, W., Hus, M., Machnicki, M., Stokłosa, T."In vivo, <em>ex vivo</em> and <em>in vitro</em> dasatinib activity in chronic lymphocytic leukemia". Oncology Letters 21.4 (2021): 285.
Chicago
Giannopoulos, K., Karczmarczyk, A., Karp, M., Bojarska‑Junak, A., Kosior, K., Kowal, M., Tomczak, W., Hus, M., Machnicki, M., Stokłosa, T."In vivo, <em>ex vivo</em> and <em>in vitro</em> dasatinib activity in chronic lymphocytic leukemia". Oncology Letters 21, no. 4 (2021): 285. https://doi.org/10.3892/ol.2021.12546