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. 2024 May 21;5(5):101565.
doi: 10.1016/j.xcrm.2024.101565.

Integrated functional genomic screening to bypass TKI resistance in chronic myeloid leukemia

Tumas Beinortas  1 , Brian J P Huntly  2
Affiliations

Integrated functional genomic screening to bypass TKI resistance in chronic myeloid leukemia

Tumas Beinortas et al. Cell Rep Med. .

Abstract

CML is readily treatable with tyrosine kinase inhibitors (TKIs); however, resistance occurs, with the disease curable in only ∼15%-20% of patients. Using integrated functional genomics, Adnan Awad et al.1 identify agents effective against CML stem cells and describe mechanisms underlying TKI resistance.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Figures

Figure 1
Figure 1
Integrative functional genomics in CML to treat BCR::ABL-independent resistance and increase TFR Adnan Awad and colleagues combine genome-wide CRISPR screening of CML cell lines under selective pressure of TKI therapy with combinatorial drug screening in LSCs from individual CML patients to identify (A) personalized strategies to eradicate LSCs and achieve TFR and (B) novel effective combinations to restore response in resistant patients. DSRT, drug sensitivity and resistance testing; MMR, major molecular response.
See this image and copyright information in PMC

References

    1. Awad S.A., Dufva O., Klievink J., Karjalainen E., Ianevski A., Pietarinen P., Kim D., Potdar S., Wolf M., Lotfi K., et al. Integrated drug profiling and CRISPR screening identify BCR::ABL1 independent vulnerabilities in chronic myeloid leukemia. Cell Rep. Med. 2024;5 - PubMed
    1. Hochhaus A., Ernst T. TKI discontinuation in CML: how do we make more patients eligible? How do we increase the chances of a successful treatment-free remission? Hematology Am. Soc. Hematol. Educ. Program. 2021;2021:106–112. - PMC - PubMed
    1. Mojtahedi H., Yazdanpanah N., Rezaei N. Chronic myeloid leukemia stem cells: targeting therapeutic implications. Stem Cell Res. Ther. 2021;12:603. - PMC - PubMed
    1. Lewis M., Prouzet-Mauléon V., Lichou F., Richard E., Iggo R., Turcq B., Mahon F. A genome-scale CRISPR knock-out screen in chronic myeloid leukemia identifies novel drug resistance mechanisms along with intrinsic apoptosis and MAPK signaling. Cancer Med. 2020;9:6739–6751. - PubMed
    1. Malani D., Kumar A., Brück O., Kontro M., Yadav B., Hellesøy M., Kuusanmäki H., Dufva O., Kankainen M., Eldfors S., et al. Implementing a Functional Precision Medicine Tumor Board for Acute Myeloid Leukemia. Cancer Discov. 2022;12:388–401. - PMC - PubMed

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