TY - JOUR
T1 - A non-cell-autonomous role for Pml in the maintenance of leukemia from the niche
AU - Guarnerio, Jlenia
AU - Mendez, Lourdes Maria
AU - Asada, Noboru
AU - Menon, Archita Venugopal
AU - Fung, Jacqueline
AU - Berry, Kelsey
AU - Frenette, Paul S.
AU - Ito, Keisuke
AU - Pandolfi, Pier Paolo
N1 - Funding Information:
We thank Lauren Southwood, Kaitlyn Doherty, and Elizabeth Stack for their insightful editing, and all members of the Pandolfi lab for critical discussion. Grants Support: Jlenia Guarnerio was supported by a post-doctoral fellowship from American-Italian Cancer Foundation for the execution of this work. This work has been supported by the NIH grants (R01-CA142874 and R35CA197529 to Pier Paolo Pandolfi and R01 DK056638 to P.S.F.).
Publisher Copyright:
© 2017 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Disease recurrence after therapy, due to the persistence of resistant leukemic cells, represents a fundamental problem in the treatment of leukemia. Elucidating the mechanisms responsible for the maintenance of leukemic cells, before and after treatment, is therefore critical to identify curative modalities. It has become increasingly clear that cell-autonomous mechanisms are not solely responsible for leukemia maintenance. Here, we report a role for Pml in mesenchymal stem cells (MSCs) in supporting leukemic cells of both CML and AML. Mechanistically, we show that Pml regulates pro-inflammatory cytokines within MSCs, and that this function is critical in sustaining CML-KLS and AML ckit+ leukemic cells non-cell autonomously.
AB - Disease recurrence after therapy, due to the persistence of resistant leukemic cells, represents a fundamental problem in the treatment of leukemia. Elucidating the mechanisms responsible for the maintenance of leukemic cells, before and after treatment, is therefore critical to identify curative modalities. It has become increasingly clear that cell-autonomous mechanisms are not solely responsible for leukemia maintenance. Here, we report a role for Pml in mesenchymal stem cells (MSCs) in supporting leukemic cells of both CML and AML. Mechanistically, we show that Pml regulates pro-inflammatory cytokines within MSCs, and that this function is critical in sustaining CML-KLS and AML ckit+ leukemic cells non-cell autonomously.
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U2 - 10.1038/s41467-017-02427-x
DO - 10.1038/s41467-017-02427-x
M3 - Article
C2 - 29302031
AN - SCOPUS:85040223273
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 66
ER -