PICH deficiency limits the progression of MYC-induced B-cell lymphoma
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PICH deficiency limits the progression of MYC-induced B-cell lymphoma. / Castejón-Griñán, María; Albers, Eliene; Simón-Carrasco, Lucía; Aguilera, Paula; Sbroggio, Mauro; Pladevall-Morera, David; Ingham, Andreas; Lim, Ernest; Guillen-Benitez, Alba; Pietrini, Elena; Lisby, Michael; Hickson, Ian D.; Lopez-Contreras, Andres J.
I: Blood Cancer Journal, Bind 14, Nr. 1, 16, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - PICH deficiency limits the progression of MYC-induced B-cell lymphoma
AU - Castejón-Griñán, María
AU - Albers, Eliene
AU - Simón-Carrasco, Lucía
AU - Aguilera, Paula
AU - Sbroggio, Mauro
AU - Pladevall-Morera, David
AU - Ingham, Andreas
AU - Lim, Ernest
AU - Guillen-Benitez, Alba
AU - Pietrini, Elena
AU - Lisby, Michael
AU - Hickson, Ian D.
AU - Lopez-Contreras, Andres J.
N1 - Publisher Copyright: © 2024, The Author(s).
PY - 2024
Y1 - 2024
N2 - Plk1-interacting checkpoint helicase (PICH) is a DNA translocase involved in resolving ultrafine anaphase DNA bridges and, therefore, is important to safeguard chromosome segregation and stability. PICH is overexpressed in various human cancers, particularly in lymphomas such as Burkitt lymphoma, which is caused by MYC translocations. To investigate the relevance of PICH in cancer development and progression, we have combined novel PICH-deficient mouse models with the Eμ-Myc transgenic mouse model, which recapitulates B-cell lymphoma development. We have observed that PICH deficiency delays the onset of MYC-induced lymphomas in Pich heterozygous females. Moreover, using a Pich conditional knockout mouse model, we have found that Pich deletion in adult mice improves the survival of Eμ-Myc transgenic mice. Notably, we show that Pich deletion in healthy adult mice is well tolerated, supporting PICH as a suitable target for anticancer therapies. Finally, we have corroborated these findings in two human Burkitt lymphoma cell lines and we have found that the death of cancer cells was accompanied by chromosomal instability. Based on these findings, we propose PICH as a potential therapeutic target for Burkitt lymphoma and for other cancers where PICH is overexpressed.
AB - Plk1-interacting checkpoint helicase (PICH) is a DNA translocase involved in resolving ultrafine anaphase DNA bridges and, therefore, is important to safeguard chromosome segregation and stability. PICH is overexpressed in various human cancers, particularly in lymphomas such as Burkitt lymphoma, which is caused by MYC translocations. To investigate the relevance of PICH in cancer development and progression, we have combined novel PICH-deficient mouse models with the Eμ-Myc transgenic mouse model, which recapitulates B-cell lymphoma development. We have observed that PICH deficiency delays the onset of MYC-induced lymphomas in Pich heterozygous females. Moreover, using a Pich conditional knockout mouse model, we have found that Pich deletion in adult mice improves the survival of Eμ-Myc transgenic mice. Notably, we show that Pich deletion in healthy adult mice is well tolerated, supporting PICH as a suitable target for anticancer therapies. Finally, we have corroborated these findings in two human Burkitt lymphoma cell lines and we have found that the death of cancer cells was accompanied by chromosomal instability. Based on these findings, we propose PICH as a potential therapeutic target for Burkitt lymphoma and for other cancers where PICH is overexpressed.
U2 - 10.1038/s41408-024-00979-y
DO - 10.1038/s41408-024-00979-y
M3 - Journal article
C2 - 38253636
AN - SCOPUS:85182809034
VL - 14
JO - Blood Cancer Journal
JF - Blood Cancer Journal
SN - 2044-5385
IS - 1
M1 - 16
ER -
ID: 381062007