A non-cell-autonomous role for Pml in the maintenance of leukemia from the niche

Pml 在维持白血病微环境方面发挥非细胞自主作用

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作者:Jlenia Guarnerio, Lourdes Maria Mendez, Noboru Asada, Archita Venugopal Menon, Jacqueline Fung, Kelsey Berry, Paul S Frenette, Keisuke Ito, Pier Paolo Pandolfi

Abstract

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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