Treatment-Free Remission in Chronic Myeloid Leukemia and New Approaches by Targeting Leukemia Stem Cells

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Nov 15

PMID 34778088

Citations 10

Authors

Yilin Chen

Jing Zou

Fanjun Cheng

Weiming Li

Affiliations

Soon will be listed here.

Abstract

The therapeutic landscape for chronic myeloid leukemia (CML) has improved significantly with the approval of tyrosine kinase inhibitors (TKIs) for therapeutic use. Most patients with optimal responses to TKIs can have a normal life expectancy. Treatment-free remission (TFR) after discontinuing TKI has increasingly become a new goal for CML treatment. However, TKI only "control" CML, and relapse after discontinuation has become a key factor hindering patient access to attempt TFR. In this study, we reviewed studies on TKI discontinuation, including both first and second-generation TKI. We also reviewed predictors of relapse, new monitoring methods, and strategies targeting leukemic stem cells.

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References

Zhang H, Li H, Xi H, Li S . HIF1α is required for survival maintenance of chronic myeloid leukemia stem cells. Blood. 2012; 119(11):2595-607. PMC: 3311277. DOI: 10.1182/blood-2011-10-387381. View

Gallipoli P, Pellicano F, Morrison H, Laidlaw K, Allan E, Bhatia R . Autocrine TNF-α production supports CML stem and progenitor cell survival and enhances their proliferation. Blood. 2013; 122(19):3335-9. PMC: 3953090. DOI: 10.1182/blood-2013-02-485607. View

Michel C, Burchert A, Hochhaus A, Saussele S, Neubauer A, Lauseker M . Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV. Haematologica. 2018; 104(5):955-962. PMC: 6518910. DOI: 10.3324/haematol.2018.206797. View

Lim S, Saw T, Zhang M, Janes M, Nacro K, Hill J . Targeting of the MNK-eIF4E axis in blast crisis chronic myeloid leukemia inhibits leukemia stem cell function. Proc Natl Acad Sci U S A. 2013; 110(25):E2298-307. PMC: 3690864. DOI: 10.1073/pnas.1301838110. View

DAdda M, Farina M, Schieppati F, Borlenghi E, Bottelli C, Cerqui E . The e13a2 BCR-ABL transcript negatively affects sustained deep molecular response and the achievement of treatment-free remission in patients with chronic myeloid leukemia who receive tyrosine kinase inhibitors. Cancer. 2019; 125(10):1674-1682. DOI: 10.1002/cncr.31977. View

Shah N . NCCN Guidelines Updates: Discontinuing TKI Therapy in the Treatment of Chronic Myeloid Leukemia. J Natl Compr Canc Netw. 2019; 17(5.5):611-613. DOI: 10.6004/jnccn.2019.5013. View

Falkenberg K, Johnstone R . Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discov. 2014; 13(9):673-91. DOI: 10.1038/nrd4360. View

Rahman M, Saha S, Rahman M, Uddin M, Uddin M, Pang M . Molecular Insights Into Therapeutic Potential of Autophagy Modulation by Natural Products for Cancer Stem Cells. Front Cell Dev Biol. 2020; 8:283. PMC: 7193248. DOI: 10.3389/fcell.2020.00283. View

Sadovnik I, Hoelbl-Kovacic A, Herrmann H, Eisenwort G, Cerny-Reiterer S, Warsch W . Identification of CD25 as STAT5-Dependent Growth Regulator of Leukemic Stem Cells in Ph+ CML. Clin Cancer Res. 2015; 22(8):2051-61. PMC: 4817228. DOI: 10.1158/1078-0432.CCR-15-0767. View

10.

Ruiz M, Sanchez M, Bonecker S, Furtado C, Koile D, Yankilevich P . miRNome profiling of LSC-enriched CD34CD38CD26 fraction in Ph CML-CP samples from Argentinean patients: a potential new pharmacogenomic tool. Front Pharmacol. 2021; 11:612573. PMC: 7869017. DOI: 10.3389/fphar.2020.612573. View

11.

Ross D, Pagani I, Shanmuganathan N, Kok C, Seymour J, Mills A . Long-term treatment-free remission of chronic myeloid leukemia with falling levels of residual leukemic cells. Leukemia. 2018; 32(12):2572-2579. DOI: 10.1038/s41375-018-0264-0. View

12.

Gottschalk A, Glauche I, Cicconi S, Clark R, Roeder I . Molecular monitoring during dose reduction predicts recurrence after TKI cessation in CML. Blood. 2020; 135(10):766-769. DOI: 10.1182/blood.2019003395. View

13.

Rea D, Nicolini F, Tulliez M, Guilhot F, Guilhot J, Guerci-Bresler A . Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2016; 129(7):846-854. DOI: 10.1182/blood-2016-09-742205. View

14.

Zhou H, Mak P, Mu H, Mak D, Zeng Z, Cortes J . Combined inhibition of β-catenin and Bcr-Abl synergistically targets tyrosine kinase inhibitor-resistant blast crisis chronic myeloid leukemia blasts and progenitors in vitro and in vivo. Leukemia. 2017; 31(10):2065-2074. PMC: 5628102. DOI: 10.1038/leu.2017.87. View

15.

Cea M, Cagnetta A, Nencioni A, Gobbi M, Patrone F . New insights into biology of chronic myeloid leukemia: implications in therapy. Curr Cancer Drug Targets. 2013; 13(7):711-23. DOI: 10.2174/15680096113139990085. View

16.

Hochhaus A, Baccarani M, Silver R, Schiffer C, Apperley J, Cervantes F . European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020; 34(4):966-984. PMC: 7214240. DOI: 10.1038/s41375-020-0776-2. View

17.

Radich J, Hochhaus A, Masszi T, Hellmann A, Stentoft J, Gomez Casares M . Treatment-free remission following frontline nilotinib in patients with chronic phase chronic myeloid leukemia: 5-year update of the ENESTfreedom trial. Leukemia. 2021; 35(5):1344-1355. PMC: 8102196. DOI: 10.1038/s41375-021-01205-5. View

18.

Takahashi N, Tauchi T, Kitamura K, Miyamura K, Saburi Y, Hatta Y . Deeper molecular response is a predictive factor for treatment-free remission after imatinib discontinuation in patients with chronic phase chronic myeloid leukemia: the JALSG-STIM213 study. Int J Hematol. 2017; 107(2):185-193. DOI: 10.1007/s12185-017-2334-x. View

19.

Rea D, Henry G, Khaznadar Z, Etienne G, Guilhot F, Nicolini F . Natural killer-cell counts are associated with molecular relapse-free survival after imatinib discontinuation in chronic myeloid leukemia: the IMMUNOSTIM study. Haematologica. 2017; 102(8):1368-1377. PMC: 6643734. DOI: 10.3324/haematol.2017.165001. View

20.

Austin G, Knight K, Bell J, Carter A, Heartin E, Watson D . The effect on lymphocyte subsets of decreasing/stopping tyrosine kinase inhibitor therapy in chronic myeloid leukaemia: data from the DESTINY trial. Br J Haematol. 2018; 185(4):791-793. DOI: 10.1111/bjh.15629. View