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PP2A-activating drugs selectively eradicate TKI-resistant chronic myeloid leukemic stem cells
Open accessAbstract
The success of tyrosine kinase inhibitors (TKIs) in treating chronic myeloid leukemia (CML) depends on the requirement for BCR-ABL1 kinase activity in CML progenitors. However, CML quiescent HSCs are TKI resistant and represent a BCR-ABL1 kinase-independent disease reservoir. Here we have shown that persistence of leukemic HSCs in BM requires inhibition of the tumor suppressor protein phosphatase 2A (PP2A) and expression--but not activity--of the BCR-ABL1 oncogene. Examination of HSCs from CML patients and healthy individuals revealed that PP2A activity was suppressed in CML compared with normal HSCs. TKI-resistant CML quiescent HSCs showed increased levels of BCR-ABL1, but very low kinase activity. BCR-ABL1 expression, but not kinase function, was required for recruitment of JAK2, activation of a JAK2/β-catenin survival/self-renewal pathway, and inhibition of PP2A. PP2A-activating drugs (PADs) markedly reduced survival and self-renewal of CML quiescent HSCs, but not normal quiescent HSCs, through BCR-ABL1 kinase-independent and PP2A-mediated inhibition of JAK2 and β-catenin. This led to suppression of human leukemic, but not normal, HSC/progenitor survival in BM xenografts and interference with long-term maintenance of BCR-ABL1-positive HSCs in serial transplantation assays. Targeting the JAK2/PP2A/β-catenin network in quiescent HSCs with PADs (e.g., FTY720) has the potential to treat TKI-refractory CML and relieve lifelong patient dependence on TKIs.
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Cites
A role for Wnt signalling in self-renewal of haematopoietic stem cells
Reya, T., Duncan, A. W., Ailles, L., Domen, J., Scherer, D. C., Willert, K., Hintz, L., Nusse, R., & Weissman, I. L. (2003) · Nature · doi:10.1038/nature01593 · Cited by 2,159
Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML
Jamieson, C. H. M., Ailles, L. E., Dylla, S. J., Muijtjens, M., Jones, C., Zehnder, J. L., Gotlib, J., Li, K., Manz, M. G., Keating, A., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040258 · Cited by 1,485 · cited 1×
“The existence of a JAK2–β-catenin pathway requiring BCR-ABL1 expression, but not its activity, does not contradict the BCR-ABL1 kinase–dependent β-catenin induction/stabilization observed in CML progenitors (38, 39).”
BackgroundCorbin, A. S., Agarwal, A., Loriaux, M., Cortes, J., Deininger, M. W., & Druker, B. J. (2011) · Journal of Clinical Investigation · doi:10.1172/jci35721 · Cited by 765
Self-citationCopland, M., Hamilton, A., Elrick, L. J., Baird, J. W., Allan, E. K., Jordanides, N., Barow, M., Mountford, J. C., & Holyoake, T. L. (2006) · Blood · doi:10.1182/blood-2005-07-2947 · Cited by 635
Self-citationSkorski, T., Bellacosa, A., Nieborowska‐Skorska, M., Majewski, M., Martinez, R., Choi, J. K., Trotta, R., Wlodarski, P., Perrotti, D., Chan, T. O., et al. (1997) · The EMBO Journal · doi:10.1093/emboj/16.20.6151 · Cited by 567
Self-citationWunderlich, M., Chou, F.-S., Link, K. A., Mizukawa, B., Perry, R. L., Carroll, M., & Mulloy, J. C. (2010) · Leukemia · doi:10.1038/leu.2010.158 · Cited by 415
Self-citationProtein phosphatase 2A: a target for anticancer therapy
Perrotti, D., & Neviani, P. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70558-2 · Cited by 400
Self-citationRac2 GTPase deficiency depletes BCR-ABL+ leukemic stem cells and progenitors in vivo
Sengupta, A., Arnett, J., Dunn, S., Williams, D. A., & Cancelas, J. A. (2010) · Blood · doi:10.1182/blood-2009-10-247437 · Cited by 52
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Abraham, S. A., Hopcroft, L. E. M., Carrick, E., Drotar, M. E., Dunn, K., Williamson, A. J. K., Korfi, K., Baquero, P., Park, L. E., Scott, M. T., et al. (2016) · Nature · doi:10.1038/nature18288 · Cited by 225
Self-citationRuvolo, P. P. (2016) · BBA Clinical · doi:10.1016/j.bbacli.2016.08.002 · Cited by 143
Non-genomic mechanisms of protein phosphatase 2A (PP2A) regulation in cancer
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Metadata
- Authors
- Neviani, P., Harb, J. G., Oaks, J. J., Santhanam, R., Walker, C. J., Ellis, J. J., Ferenchak, G., Dorrance, A. M., Paisie, C. A., Eiring, A. M., Ma, Y., Mao, H. C., Zhang, B., Wunderlich, M., May, P. C., Sun, C., Saddoughi, S. A., Bielawski, J., Blum, W., Klisovic, R. B., Solt, J. A., Byrd, J. C., Volinia, S., Cortes, J., Huettner, C. S., Koschmieder, S., Holyoake, T. L., Devine, S., Caligiuri, M. A., Croce, C. M., Garzon, R., Ogretmen, B., Arlinghaus, R. B., Chen, C.-S., Bittman, R., Hokland, P., Roy, D.-C., Milojkovic, D., Apperley, J., Goldman, J. M., Reid, A., Mulloy, J. C., Bhatia, R., Marcucci, G., & Perrotti, D.
- Venue
- Journal of Clinical Investigation
- Published
- 2013-09-03
- Volume
- 123
- Issue
- 10
- Pages
- 4144-4157
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2021635600
- Cited by
- 221
- References
- 8
- FWCI
- 17.06
- Type
- journal article
- Language
- en
- Open access
- green
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- Neviani, P., Harb, J. G., Oaks, J. J., Santhanam, R., Walker, C. J., Ellis, J. J., Ferenchak, G., Dorrance, A. M., Paisie, C. A., Eiring, A. M., Ma, Y., Mao, H. C., Zhang, B., Wunderlich, M., May, P. C., Sun, C., Saddoughi, S. A., Bielawski, J., Blum, W., . . . Perrotti, D. (2013). PP2A-activating drugs selectively eradicate TKI-resistant chronic myeloid leukemic stem cells. Journal of Clinical Investigation. https://doi.org/10.1172/jci68951
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