Aurora B kinase as a therapeutic target in acute lymphoblastic leukemia

Goto, Hiroaki; Yoshino, Yuki; Ito, Mieko; Nagai, J.; Kumamoto, Tadashi; Inukai, Takesi; Sakurai, Yukari; Miyagawa, Naoyuki; Keino, Dai; Yokosuka, Tomoko; Iwasaki, Fuminori; Hamanoue, Satoshi; Shiomi, Masae; Goto, Shoko

doi:10.1007/s00280-020-04045-9

Cited by 12 publications

(12 citation statements)

References 37 publications

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“…Recent evidence elucidates a role for AURKB in inhibiting proteasomal degradation of MYC, thus stabilizing this oncogenic protein (140). In vitro treatment of T-ALL cells with the AURKB inhibitor barasertib (AZD1152) leads to reduced MYC protein levels (140) and enhanced cell death (140,141). Furthermore, AZD1152 can act in synergy with vincristine (140).…”

Section: Other Promising Targeted Treatments In Developmentmentioning

confidence: 99%

T-cell Acute Lymphoblastic Leukemia: A Roadmap to Targeted Therapies

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Canté-Barrett

et al. 2021

Blood Cancer Discovery

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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy characterized by aberrant proliferation of immature thymocytes. Despite an overall survival of 80% in the pediatric setting, 20% of patients with TALL ultimately die from relapsed or refractory disease. Therefore, there is an urgent need for novel therapies. Molecular genetic analyses and sequencing studies have led to the identification of recurrent TALL genetic drivers. This review summarizes the main genetic drivers and targetable lesions of TALL and gives a comprehensive overview of the novel treatments for patients with TALL that are currently under clinical investigation or that are emerging from preclinical research. Significance: TALL is driven by oncogenic transcription factors that act along with secondary acquired mutations. These lesions, together with active signaling pathways, may be targeted by therapeutic agents. Bridging research and clinical practice can accelerate the testing of novel treatments in clinical trials, offering an opportunity for patients with poor outcome.

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Section: Other Promising Targeted Treatments In Developmentmentioning

confidence: 99%

T-cell Acute Lymphoblastic Leukemia: A Roadmap to Targeted Therapies

Cordó

Zwet

Canté-Barrett

et al. 2021

Blood Cancer Discovery

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“…After a 4‐day incubation period, the cell viability of each well was measured using the Cell Titer‐Glo luminescent assay (Promega, Madison, WI, USA). To compare drug sensitivities between samples the DES 6,7 was utilised as follows: DES = {(100 − % survival at 5 −3 dilution) × ln(125) + (100 − % survival at 5 −2 dilution) × ln(25) + (100 − % survival at 5–1 dilution) × ln(5) + (100 − % survival at no dilution)/(ln[125] + ln[25] + ln[5] + 1)}. A DES of 100 indicated that the vector killed all the cells at every tested concentration, whereas a DES of zero indicated that the drug had no effect.…”

Section: Methodsmentioning

confidence: 99%

“…To evaluate the drug sensitivity of TAM blasts, DST was performed as previously reported. 6 Briefly, cryopreserved PB cells were seeded at 1 9 10 4 live cells/10 µl onto a 384-well plate that was preloaded with 10 µl of culture medium containing one of 41 drugs at four serially diluted concentrations (9 1, 9 5 À1 , 9 5 À2 , 9 5 À3 ). The list of drugs and final concentrations that were used in the DST are shown in Supplemental Table SI.…”

Section: High-throughput Drug Sensitivity Screeningmentioning

confidence: 99%

Using the in vitro drug sensitivity test to identify candidate treatments for transient abnormal myelopoiesis

et al. 2021

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Approximately 20% of patients with transient abnormal myelopoiesis (TAM) die due to hepatic or multiorgan failure. To identify potential new treatments for TAM, we performed in vitro drug sensitivity testing (DST) using the peripheral blood samples of eight patients with TAM. DST screened 41 agents for cytotoxic properties against TAM blasts. Compared with the reference samples of healthy subjects, TAM blasts were more sensitive to glucocorticoids, the mitogen-activated protein kinase kinase (MAP2K) inhibitor trametinib, and cytarabine. Our present results support the therapeutic potential of glucocorticoids and the role of the RAS/ MAP2K signalling pathway in TAM pathogenesis.

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“…Drug sensitivity screening, which we previously performed in leukemic cells, was performed to evaluate the drug sensitivity of SMARCB1/INI1-de cient tumor cell lines [15]. Brie y, 80 agents with several different classes of action were dissolved in DMSO or deionized water according to the manufacturer's instructions, and diluted in FBS-free RPMI1640.…”

Section: Drug Sensitivity Screeningmentioning

confidence: 99%

YM155 and chrysin cooperatively suppress survivin expression in SMARCB1/INI1-deficient tumor cells

et al. 2022

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SMARCB1/INI1 de ciency is seen in several malignant tumors including malignant rhabdoid tumor (MRT), a highly aggressive pediatric malignancy. Loss of SMARCB1/INI1 function alters diverse oncogenic cellular signals, making it di cult to discover effective targeting therapy. By utilizing an in vitro drug screening system, effective therapeutic agents against SMARCB1/INI1-de cient tumors were explored in this study.In the in vitro drug sensitivity test, 80 agents with various actions were screened for their cytotoxicity in a panel of ve SMARCB1/INI1-de cient tumor cell lines. The combination effect was screened based on the Bliss independent model. The growth inhibitory effect was determined in both the conventional twodimensional culture and the collagen-embedded three-dimensional culture system. Survivin expression after agent exposure was determined by Western blot analysis.All ve cell lines were found to be sensitive to YM155, a selective survivin inhibitor. In the drug combination screening, YM155 showed additive to synergistic effects with various agents including chrysin. Chrysin enhanced YM155-induced apoptosis, but not mitochondrial depolarization upon exposure of SMARCB1/INI1-de cient tumor cells to the two agents for 6 hours. YM155 and chrysin synergistically suppressed survivin expression, especially in TTN45 cells in which such suppression was observed as early as 6 hours after exposure to the two agents.Survivin is suggested to be a therapeutic target in MRT and other SMARCB1/INI1-de cient tumors. Chrysin, a avone that is widely distributed in plants, cooperatively suppressed survivin expression and enhanced the cytotoxicity of YM155.

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Aurora B kinase as a therapeutic target in acute lymphoblastic leukemia

Cited by 12 publications

References 37 publications

T-cell Acute Lymphoblastic Leukemia: A Roadmap to Targeted Therapies

T-cell Acute Lymphoblastic Leukemia: A Roadmap to Targeted Therapies

Using the in vitro drug sensitivity test to identify candidate treatments for transient abnormal myelopoiesis

YM155 and chrysin cooperatively suppress survivin expression in SMARCB1/INI1-deficient tumor cells

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