Mardilovich, Katerina and Naylor, Gregory and Julian, Linda and Phinichkusolchit, Narisa and Keeshan, Karen and Blyth, Karen and Olson, Michael F. (2024) Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice. Disease Models and Mechanisms, 17 (5): dmm050631. ISSN 1754-8403

Abstract

Apoptosis is characterized by membrane blebbing and apoptotic body formation. Caspase cleavage of ROCK1 generates an active fragment that promotes actin-myosin mediated contraction and membrane blebbing during apoptosis. Expression of caspase-resistant non-cleavable ROCK1 (Rock1 NC) prolonged survival of mice that rapidly develop B cell lymphomas due to Eµ-Myc transgene expression. Eµ-Myc; Rock1 NC mice had significantly fewer bone marrow cells relative to Eµ-Myc mice expressing wild-type ROCK1 (Rock1 WT), which was associated with altered cell cycle profiles. Circulating macrophage numbers were lower in Eµ-Myc; Rock1 NC mice, but there were higher levels of bone marrow macrophages, consistent with spontaneous cell death in Eµ-Myc; Rock1 NC mice bone marrows being more inflammatory. Rock1 WT recipient mice transplanted with pre-neoplastic Eµ-Myc; Rock1 NC bone marrow cells survived longer than mice transplanted with Eµ-Myc; Rock1 WT cells, indicating that the survival benefit was intrinsic to the Eµ-Myc; Rock1 NC bone marrow cells. The results suggest that the apoptotic death of Eµ-Myc; Rock1 NC cells generates a proliferation-suppressive microenvironment in bone marrows that reduces cell numbers and prolongs B cell lymphoma mouse survival.

People
Mardilovich, Katerina
Author

Mardilovich, Katerina and Naylor, Gregory and Julian, Linda and Phinichkusolchit, Narisa and Keeshan, Karen and Blyth, Karen and Olson, Michael F. (2024) Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice. Disease Models and Mechanisms, 17 (5): dmm050631. ISSN 1754-8403

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Naylor, Gregory
Author

Mardilovich, Katerina and Naylor, Gregory and Julian, Linda and Phinichkusolchit, Narisa and Keeshan, Karen and Blyth, Karen and Olson, Michael F. (2024) Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice. Disease Models and Mechanisms, 17 (5): dmm050631. ISSN 1754-8403

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Julian, Linda
Author

Mardilovich, Katerina and Naylor, Gregory and Julian, Linda and Phinichkusolchit, Narisa and Keeshan, Karen and Blyth, Karen and Olson, Michael F. (2024) Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice. Disease Models and Mechanisms, 17 (5): dmm050631. ISSN 1754-8403

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Phinichkusolchit, Narisa
Author

Mardilovich, Katerina and Naylor, Gregory and Julian, Linda and Phinichkusolchit, Narisa and Keeshan, Karen and Blyth, Karen and Olson, Michael F. (2024) Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice. Disease Models and Mechanisms, 17 (5): dmm050631. ISSN 1754-8403

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Keeshan, Karen
Author

Mardilovich, Katerina and Naylor, Gregory and Julian, Linda and Phinichkusolchit, Narisa and Keeshan, Karen and Blyth, Karen and Olson, Michael F. (2024) Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice. Disease Models and Mechanisms, 17 (5): dmm050631. ISSN 1754-8403

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Blyth, Karen
Author

Elbassioni, Ali Ali Mohamed and Raheem, Anmar A. and Song, Jian and Johnston, Alexander S. and Trivett, Cara and Lin, Hong and Zhang, Haobo and Bradley, Ashley and Higgins, Erin and Mooney, Leanne and Koay, Yen Chin and O'Toole, Dylan and Herzyk, Pawel and Nixon, Colin and Blyth, Karen and O'Sullivan, John F. and Lang, Ninian N. and Berry, Colin and Braun, Thomas and Schiattarella, Gabriele G. and Giacca, Mauro and McBride, Martin W. and Nicklin, Stuart A. and Cameron, Ewan R. and Loughrey, Christopher M. and MacDonald, Eilidh A. (2025) Targeting Runx1 protects against heart failure with preserved ejection fraction. bioRxiv.

Strathearn, Lauren S. and Spender, Lindsay C. and Schoenherr, Christina and Mason, Susan and Edwards, Ruaridh and Blyth, Karen and Inman, Gareth (2024) C1orf106 (INAVA) is a SMAD3-dependent TGF-β target gene that promotes clonogenicity and correlates with poor prognosis in breast cancer. Cells, 13 (18): 1530. ISSN 2073-4409

Mardilovich, Katerina and Naylor, Gregory and Julian, Linda and Phinichkusolchit, Narisa and Keeshan, Karen and Blyth, Karen and Olson, Michael F. (2024) Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice. Disease Models and Mechanisms, 17 (5): dmm050631. ISSN 1754-8403

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Olson, Michael F.
Author

Mardilovich, Katerina and Naylor, Gregory and Julian, Linda and Phinichkusolchit, Narisa and Keeshan, Karen and Blyth, Karen and Olson, Michael F. (2024) Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice. Disease Models and Mechanisms, 17 (5): dmm050631. ISSN 1754-8403

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