Simplifying procedure for prediction of resistance risk in CML patients — Test of sensitivity to TKI ex vivo

Žáčková, Markéta; Macháčková-Lopotová, Tereza; Ondrackova, Zuzana; Kuželová, Kateřina; Klamová, Hana; Moravcová, Jana

doi:10.1016/j.bcmd.2016.03.005

Cited by 4 publications

(7 citation statements)

References 55 publications

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“…The major outcomes were that none of our patients reported any significant side-effects despite the fact that the length of treatment was from 3-10 years with 90% having been treated for more than 6years. These outcomes are in agreement with a number of local reports from Saudi Arabia [4][5][6][7][8][9][10][11][12][13][14][15][16] .…”

Section: Preparation Of Mononuclear Cells For Culture and Cfu-gm Cultursupporting

confidence: 81%

Imatinib reduces proliferation of leukemic cells in vitro

Alanazi

Alanazi²,

Alanazi

et al. 2017

Bangladesh J Med Sci

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Introduction: Philadelphia chromosome is a cytogenetic marker for chronic myeloid leukemia (CML). The main aims of this study were to assess the positive responses, side-effects and survival of CML patients treated with imatinib mesylate. Methods: All recently diagnosed CML patients who were treated with imatinib were recruited to this study. We investigated hematological and cytogenetic parameters by CBC, FISH and RT-PCR individually. Results: Of the 10 cases, 7 (70%) were males and 3 (30%) were female. Four (40%) of the cases were analyzed retrospectively and 8 cases (80%) exhibited general exhaustion (75%), fever (80%), and splenomegaly (80%). Indications of bleeding and rashes were rarely seen at presentation. The majority of the patients had a generally low risk profile (70%), 30% had intermediate risk; with no subjects exhibiting high risk CML, 9 subjects (90%) were in remission.

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Section: Preparation Of Mononuclear Cells For Culture and Cfu-gm Cultursupporting

confidence: 81%

Imatinib reduces proliferation of leukemic cells in vitro

Alanazi

Alanazi²,

Alanazi

et al. 2017

Bangladesh J Med Sci

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“…As we and others have previously shown (47–49), results of in vitro/ex vivo cultivation of isolated patient leukocytes with TKIs correlate well with therapy results and are of a great prognostic value. Similarly, in vitro experiments with CK2 inhibitors could predict the role of CK2 in resistance to TKI and thus a possibility to target CK2 kinase.…”

Section: Discussionsupporting

confidence: 67%

“…Leukocytes from CML patients and healthy donors were isolated as described previously (33,49). Responses to therapy were defined according to European Leukemia Net (ELN) classification (22).…”

Section: Methodsmentioning

confidence: 99%

“…Parental cell lines were cultivated in parallel without inhibitors. All cells were incubated at 37 °C in RPMI medium with 10% fetal bovine serum and antibiotics 51,68 .…”

Section: Patient Samples and Cell Culturesmentioning

confidence: 99%

“…Western blot analyses were performed as described previously 68 . Briefly, cells were harvested, lysed in Laemmli buffer, and boiled for 10 minutes.…”

Section: Western Blottingmentioning

confidence: 99%

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Inhibition of Casein Kinase 2 induces cell death in chronic myelogenous leukemia cells resistant to tyrosine kinase inhibitors

Mitrovský

Myslivcová

Macháčková-Lopotová

et al. 2021

Preprint

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Chronic myelogenous leukemia (CML) is a myeloproliferative disease characterized by the presence of a BCR-ABL oncogene. Despite the high performance of treatment with tyrosine kinase inhibitors (TKI), about 30 % of patients develop resistance to therapy. To improve the outcome of CML therapy, the identification of new targets of treatment is needed. Here, we explored the Casein Kinase 2 (CK2) as a potential target for CML therapy. Previously, we detected increased phosphorylation of HSP90β Serine 226 in patients non-responding to TKIs imatinib and dasatinib. This site is known to be phosphorylated among others by CK2, which was also previously linked to CML resistance to imatinib. In the present work, we established six novel imatinib- and dasatinib-resistant CML cell lines and detected increased CK2 activation in all these resistant cells. A CK2 inhibitor, CX-4945, induced cell death of CML cells in both parental and resistant cell lines. In some cases, CK2 inhibition also potentiated the effects of TKI on cell metabolic activity. No effects of CK2 inhibition were observed in normal mononuclear blood cells from healthy donors and BCR-ABL negative HL60 cell line. Our data indicate that CK2 kinase supports CML cell viability even in cells with different mechanisms of resistance to TKI, and thus represents a potential target for treatment.

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