Amplifikacja BCR-ABL ma istotne znaczenie w oporności na inhibitory kinazy tyrozynowj w linii komórkowej K-562
DOI:
https://doi.org/10.12775/v10251-012-0054-2Słowa kluczowe
amplifikacja BCR-ABL, przewlekła białaczka szpikowa, oporność na cytostatyki, imatynib, inhibitory kinazy tyrozynowej, linia K-562Abstrakt
Narastająca oporność na inhibitory kinazy tyrozynowej (TKIs) jest niepokojącym problemem u pacjentów z przewlekłą białaczka szpikową (CML). Aby określić genetyczne i komórkowe mechanizmy oporności na TKIs z linii K-562 wyhodowano 9 opornych na imatynib linii komórkowych, w których przeprowadzono badania: oporności na leki, ekspresji białek oporności komórkowej oraz badania cytogenetyczne. W opornych na imatinib liniach komórkowych stwierdzono krzyżową oporność na daunorubicynę, etopozyd i cytarabinę, podczas gdy wrażliwość na dasatinib, nilotinib, cyklofosfamid, bortezomib i busulfan była zachowana. Hodowla z imatinibem zmniejszała ekspresję białka PGP i LRP ale nie wypływała na ekspresję białka MRP1. W badaniu metodą FISH w liniach opornych na imatinib w porównaniu do macierzystej linii K-562 obserwowano większą ilość sygnałów pochodzących od genów ABL, BCR oraz od genów fuzyjnych (BCR-ABL i ABL-BCR). Przeprowadzone badania wskazują, że nie mechanizmy oporności komórkowej ale amplifikacja sekwencji BCR-ABL, jest głównym mechanizmem oporności na TKIs w linii K-562.Bibliografia
Khamaisie H, Sussan S, Tal M, et al. Oleic acid is the active component in the mushroom Daedalea gibbosa inhibiting Bcr-Abl kinase autophosphorylation activity. Anticancer Res. 2011; 31 (1): 177-183.
Baccarani M, Cortes J, Pane F, et al. Chronic Myeloid Leukemia: An Update of Concepts and Management Recommendations of European LeukemiaNet. J Clin Oncol. 2009; 27 (35):6041-6051. [ http://dx.doi.org/10.1200/JCO.2009.25.0779]
Bixby D, Talpaz M. Mechanisms of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia and recent therapeutic strategies to overcome resistance. Hematology Am Soc Hematol Educ Program. 2009: 461-476.
Lahaye T, Riehm B, Berger U, et al. Response and resistance in 300 patients with BCR-ABL-positive leukemias treated with imatinib in a single center: a 4.5- year follow-up. Cancer. 2005; 103 (8): 1659-1669. [ http://dx.doi.org/10.1002/cncr.20922]
Hochhaus A, Kreil S, Corbin AS, et al. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia. 2002; 16 (11): 2190-2196.
Styczynski J, Toporski J, Wysocki M, et al. Fludarabine, treosulfan and etoposide sensitivity and the outcome of hematopoietic stem cell transplantation in childhood acute myeloid leukemia. Anticancer Res. 2007; 27 (3B): 1547-1551.
Gil L, Styczynski J, Dytfeld D, et al. Activity of bortezomib in adult de novo and relapsed acute myeloid leukemia. Anticancer Res. 2007; 27 (6B): 4021-4025.
Sierra JR, Cepero V, Giordano S. Molecular mechanisms of acquired resistance to tyrosine kinase targeted therapy. Mol Cancer. 2010; 9: 75. [ http://dx.doi.org/10.1186/1476-4598-9-75]
Suzuki M, Abe A, Imagama S, et al. BCR-ABLindependent and RAS / MAPK pathway-dependent form of imatinib resistance in Ph-positive acute lymphoblastic leukemia cell line with activation of EphB4. Eur J Haematol. 2010; 84 (3): 229-238. [ http://dx.doi.org/10.1111/j.1600-0609.2009.01387.x]
Kantarjian HM, Talpaz M, O'Brien S, et al. Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood. 2003; 101 (2): 473-475. [ http://dx.doi.org/10.1182/blood-2002-05-1451]
O'Hare T, Eide CA, Deininger MW. Bcr-Abl kinase domain mutations and the unsettled problem of Bcr- AblT315I: looking into the future of controlling drug resistance in chronic myeloid leukemia. Clin Lymphoma Myeloma. 2007; 7 Suppl 3: 120-130.
O'Hare T, Walters DK, Deininger MW, et al. AMN107: tightening the grip of imatinib. Cancer Cell. 2005; 7 (2): 117-119.
Le Blanc K, Barrett AJ, Schaffer M, et al. Lymphocyte recovery is a major determinant of outcome after matched unrelated myeloablative transplantation for myelogenous malignancies. Biol Blood Marrow Transplant. 2009; 15 (9): 1108-1115.
Santos GW. Busulfan (Bu) and cyclophosphamide (Cy) for marrow transplantation. Bone Marrow Transplant. 1989; 4 Suppl 1: 236-239.
Servida F, Soligo D, Delia D, et al. Sensitivity of human multiple myelomas and myeloid leukemias to the proteasome inhibitor I. Leukemia. 2005; 19 (12): 2324-2331. [ http://dx.doi.org/10.1038/sj.leu.2403987]
Albero MP, Vaquer JM, Andreu EJ, et al. Bortezomib decreases Rb phosphorylation and induces caspasedependent apoptosis in Imatinib-sensitive and -resistant Bcr-Abl1-expressing cells. Oncogene. 2010; 29 (22): 3276-3286.
Mackey JR, Mani RS, Selner M, et al. Functional nucleoside transporters are required for gemcitabine influx and manifestation of toxicity in cancer cell lines. Cancer Res. 1998; 58 (19): 4349-4357.
Dumontet C, Fabianowska-Majewska K, Mantincic D, et al. Common resistance mechanisms to deoxynucleoside analogues in variants of the human erythroleukaemic line K562. Br J Haematol. 1999; 106 (1): 78-85.
Kano Y, Akutsu M, Tsunoda S, et al. In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents. Blood. 2001; 97 (7):1999-2007.
Tipping AJ, Mahon FX, Zafirides G, et al. Drug responses of imatinib mesylate-resistant cells: synergism of imatinib with other chemotherapeutic drugs. Leukemia. 2002; 16 (12): 2349-2357. [ http://dx.doi.org/10.1038/sj.leu.2402775]
Tabrizi R, Mahon FX, Cony Makhoul P, et al. Resistance to daunorubicin-induced apoptosis is not completely reversed in CML blast cells by STI571. Leukemia. 2002; 16 (6): 1154-1159.
Paietta E. Classical multidrug resistance in acute myeloid leukaemia. Med Oncol. 1997; 14 (1): 53-60[ http://dx.doi.org/10.1007/BF02990947]
Zong Y, Zhou S, Sorrentino BP. Loss of P-glycoprotein expression in hematopoietic stem cells does not improve responses to imatinib in a murine model of chronic myelogenous leukemia. Leukemia. 2005; 19 (9): 1590-1596.[ http://dx.doi.org/10.1038/sj.leu.2403853]
Ferrao PT, Frost MJ, Siah S-P, et al. Overexpression of P-glycoprotein in K562 cells does not confer resistance to the growth inhibitory effects of imatinib (STI571) in vitro. Blood. 2003; 102 (13): 4499-4503.
Mahon FX, Deininger MW, Schultheis B, et al. Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance. Blood. 2000; 96 (3): 1070-1079.
Mahon F-X, Belloc F, Lagarde V, et al. MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood. 2003; 101 (6): 2368-2373.
Davies A, Jordanides NE, Giannoudis A, et al. Nilotinib concentration in cell lines and primary CD34(+) chronic myeloid leukemia cells is not mediated by active uptake or efflux by major drug transporters. Leukemia. 2009; 23 (11): 1999-2006.
Giannoudis A, Davies A, Lucas CM, et al. Effective dasatinib uptake may occur without human organic cation transporter 1 (hOCT1): implications for the treatment of imatinib-resistant chronic myeloid leukemia. Blood. 2008; 112 (8): 3348-3354.
le Coutre P, Tassi E, Varella-Garcia M, et al. Induction of resistance to the Abelson inhibitor STI571 in human leukemic cells through gene amplification. Blood. 2000; 95 (5): 1758-1766.
Weisberg E, Griffin JD. Mechanism of resistance to the ABL tyrosine kinase inhibitor STI571 in BCR/ABLtransformed hematopoietic cell lines. Blood. 2000 ;95 (11): 3498-3505.
Phan CL, Megat Baharuddin PJ, Chin LP, et al. Amplification of BCR-ABL and t(3;21) in a patient with blast crisis of chronic myelogenous leukemia. Cancer Genet Cytogenet. 2008; 180 (1): 60-64. [ http://dx.doi.org/10.1016/j.cancergencyto.2007.09.014]
Quintas-Cardama A, Kantarjian HM, Cortes JE. Mechanisms of primary and secondary resistance to imatinib in chronic myeloid leukemia. Cancer Control. 2009; 16 (2): 122-131.
Pobrania
Opublikowane
Jak cytować
Numer
Dział
Statystyki
Liczba wyświetleń i pobrań: 270
Liczba cytowań: 0