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Journals / Turkish Journal of Hematology / 2007 / Cilt: 24 - Sayı: 1

İmatinib mesilat ve fludarabin kombinasyonunun Filadelfiya kromozomu pozitif kronik myeloid lösemi hücre serileri üzerindeki sinerjistik etkisi

Synergistic effect of imatinib mesylate and fludarabine combination on Philadelphia chromosome-positive chronic myeloid leukemia cell lines

İnci ALACACIOĞLU
Bülent ÜNDAR
Fatih DEMİRKAN
G.Hayri ÖZSAN
Ali M ÖZCAN
Halil ATEŞ
Özden PİŞKİN
Pages
23–27
Publication Date
2022-11-05
DOI
—
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Based on our results, the fludarabine- based chemotherapy regimens can be used for those patients with CML blastic phase in combination with imatinib mesylate.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Fludarabine-containing combinations have additive cell killing against leukemic blasts in vitro.
📊
Key Findings & Data:In this regard, we aimed to investigate the effect of fludarabine-imatinib mesylate combination against CML blastic phase cell lines K562 and Meg-01.
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Conclusion & Impact:Based on our results, the fludarabine- based chemotherapy regimens can be used for those patients with CML blastic phase in combination with imatinib mesylate.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Fludarabine-containing combinations have additive cell killing against leukemic blasts in vitro. It has also been shown that imatinib mesylate combined with fludarabine or cladribine had an additive effect on CML CFU-GM cells. In this regard, we aimed to investigate the effect of fludarabine-imatinib mesylate combination against CML blastic phase cell lines K562 and Meg-01. XTT test was performed for proliferation and inhibition assay. According to obtained data, five different effective concentrations of each drug in 25 different combinations were tested. Results of the combination studies were analyzed with isobologram. At IC20, imatinib mesylate and fludarabine combination showed synergism and strong synergism in K562 and Meg-01 cells, respectively. At IC50 and IC75, combination indexes (CI) indicated strong synergism and synergism. Based on our results, the fludarabine- based chemotherapy regimens can be used for those patients with CML blastic phase in combination with imatinib mesylate.

Özet

In vitro koşullarda fludarabin içeren kombinasyonların lösemik blastlar üzerinde ve fludarabin ya da kladribinin imatinib mesilat ile kombinasyonlarının KML CFU-GM hücrelerine karşı aditif etkinliğe sahip oldukları gösterilmiştir. Bu gözlemlere dayanarak biz de fludarabin ve imatinib mesilat kombinasyonunun KML blastik faz hücre serileri K562 ve Meg-01 üzerine olan etkinliğini araştırmayı planladık. Proliferasyon ve inhibisyon göstergesi olarak XTT testini kullandık. Elde edilen verilere göre, her ilacın beş farklı etkin konsantrasyonu 25 farklı kombinasyon halinde test edildi. Kombinasyon çalışmalarının sonuçları izobologram ile analiz edildi. İmatinib mesilat ve fludarabinin kombinasyonunun K562 ve Meg-01 hücre serileri için IC20 kombinasyon indeksi değerleri sırası ile sinerjistik ve güçlü sinerjistik, IC50 ve IC75 değerlerinde de güçlü sinerjistik ve sinerjistik etkinliği göstermekte idi. Bu sonuçlar KML blastik fazdaki hastalar için imatinib mesilat ile kombine edilen fludarabin bazlı rejimlerin kullanılabileceğini göstermektedir.

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Cite This Article

ALACACIOĞLU, İ., ÜNDAR, B., DEMİRKAN, F., ÖZSAN, G., ÖZCAN, A. M., ATEŞ, H., PİŞKİN, Ö. (2022). İmatinib mesilat ve fludarabin kombinasyonunun Filadelfiya kromozomu pozitif kronik myeloid lösemi hücre serileri üzerindeki sinerjistik etkisi. Turkish Journal of Hematology, Cilt: 24 - Sayı: 1, 23–27. https://ajindex.com/articles/607111

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References (11)

  1. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr/abl positive cells. Nat Med 1996;2:561-6
  2. Deininger MW, Goldman JM, Lydon N, Melo JV. The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood 1997;90:3691-8
  3. Gora-Tybor J, Deininger MW, Goldman JM, Melo JV. The susceptibility of Philadelphia chromosome positive cells to FAS-mediated apoptosis is not linked to the tyrosine kinase activity of BCR/ABL. Br J Haematol 1998;103:716-20
  4. Dinndorf PA, Avramis VI, Wiersma S, Krailo MD, Liu-Mares W, Seibel NL, Sato JK, Mosher RB, Kelleher JF, Reaman GH. Phase I/II study of idarubicin given with continuous infusion fludarabine followed by continuous infusion cytarabine in children with acute leukemia: a report from the Children’s Cancer Group. J Clin Oncol 1997;15:2780–5
  5. Korycka A, Smolewski P, Robak T. The influence of farnesyl protein transferase inhibitor R115777 (Zarnestra) alone and in combination with purine nucleoside analogs on acute myeloid leukemia progenitors in vitro. Eur J Haematol 2004;73:418-26
  6. Hubeek I, Litvinova E, Peters GJ, Broekhuizen R, Haarman EG, Huismans DR, Cloos J, Zwaan CM, Fleischhack G, Creutzig U, Kaspers GJ. The effect of G-CSF on the in vitro cytotoxicity of cytarabine and fludarabine in the FLAG combination in pediatric acute myeloid leukemia. Int J Oncol 2004;25:1823-9
  7. Korycka A, Robak T. The influence of imatinib mesylate (STI571) used alone or in combination with purine nucleoside analogues on the normal and chronic myelogenous leukaemia progenitor cells in vitro. Leuk Lymphoma 2003;44:1549-55
  8. Kano Y, Akutsu M, Tsunoda S, Mano H, Sato Y, Honma Y, Furukawa Y. In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents. Blood 2001;97:1999-2007
  9. Barteneva N, Stiouf I, Donato S, Kornblau S, Domain VD, Talpaz M. Altered interferon-a responsiveness in K562 cells pretreated with abl-tyrosine kinase inhibitor CGP57148B. Blood 1999;94:272b [abstract]
  10. Thiesing JT, Ohno-Jones S, Kolibaba KS, Drucker BJ. Efficacy of an abl tyrosine kinase inhibitor in conjunction with other anti-neoplastic agents against bcr-abl positive cells. Blood 1999;94:100a [abstract]
  11. Chou TC, Zhang XG, Balog A, Su DS, Meng D, Savin K, Bertino JR, Danishefsky SJ. Desoxyepothilone B: an efficacious microtubule-