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Editorials
Figure 2. Treatment algorithm of chronic myeloid leukemia (CML) patients in future medicine incorporating next-generation sequencing (NGS)-based risk assess- ment and up-front tyrosine kinase inhibitor (TKI) drug selection.
tion of the finding before appropriate recommendations References
can be made, with the inclusion of NGS screening at ini- tial diagnosis of CML.13 Moreover, clinical risk scores at diagnosis may inform the selection of patients for NGS- based screening. Figure 2 shows an example of future therapies incorporating NGS-based testing at diagnosis in CML management. Once the diagnosis of CML is made, the next step for risk assessment will include NGS- based risk assessment in addition to clinical disease stag- ing (chronic phase vs. accelerated phase vs. blastic phase) or Sokal risk score calculation. In the case of advanced disease phase, intermediate to high Sokal risk score or those with a somatic mutation in epigenetic modifiers pathway such as ASXL1, DMNT3A, TET2 will be strong candidates for upfront therapy using the 2nd generation TKI.
In the context of somatic mutation profile in CML, some questions remain: 1) what is the role of age-related clonal hematopoiesis in the development of cardiovascu- lar toxicity following TKI therapy; 2) what is the role of somatic mutations in TKI switch for TKI resistant cases without carrying ABL1 kinase domain mutation; 3) what is the clinical relevance of somatic mutations with respect to treatment-free remission? Future studies are warranted to answer these questions so that somatic mutation pro- files can be incorporated into future CML practice not only for upfront TKI drug selection but also during follow up with TKI therapy.
There is a limitation in the study by Nteliopoulos et al.14 the study cohort did not consist of a consecutive set of patients. Thus, further study is strongly warranted to reach a clearer conclusion with a larger prospectively col- lected cohort. Upon successful validation of these data, this approach using NGS-based precision medicine will eventually be incorporated into a clinical algorithm of CML management such as future ELN recommenda- tions. Precision medicine will soon be part of our practice even in CML.
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