Chronic myeloid leukemia (CML) is a hematologic malignancy caused by a t (9;22) (q34; q11) reciprocal translocation resulting in a fusion between the breakpoint cluster region (BCR) and Abelson leukemia (ABL1) genes. Current treatment approaches are primarily focused around the use of tyrosine kinase inhibitors (TKIs), such as imatinib, which inhibit the oncogenic potential of the BCR::ABL1 fusion product that is generated as a result of the translocation. Since the approval of imatinib in 2001 by the FDA and EMA, second- and third-generation TKIs have been developed, such as nilotinib, dasatinib and bosutinib, each with varying affinities for different mutations in the kinase domain. Novel drugs continue to be developed; for example, in October 2021, asciminib, an oral, small molecule, selective allosteric inhibitor targeting the myristoyl pocket of the BCR::ABL1 tyrosine kinase, was granted FDA approval for adult patients with Ph+ CML in the chronic phase and a mutation in T315I.
Despite the availability of a large number of TKIs, there remain clinical challenges in the treatment of CML. Roughly half of all TKI treatment discontinuations are a result of TKI toxicity, and intolerance and resistance to TKIs occur frequently. Furthermore, the treatment is not curative as TKI therapy does not eliminate quiescent leukemia stem cells which are not dependent on BCR::ABL1 for survival.
Further research is needed to develop new treatment approaches which can offer improved disease control and reduced toxicity. In addition, finding ways to overcome treatment resistance is crucial to improving long-term survival outcomes. This Research Topic welcomes manuscripts on the following topics:
- Novel targeted agents for the treatment of CML
- Combination approached to the treatment of CML
- Overcoming drug resistance in CML
- Validated biomarkers for monitoring treatment response in CML
- Reducing and managing treatment-related toxicities in CML
Please note: manuscripts that are solely based on bioinformatics or computational analysis of public databases without validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Chronic myeloid leukemia (CML) is a hematologic malignancy caused by a t (9;22) (q34; q11) reciprocal translocation resulting in a fusion between the breakpoint cluster region (BCR) and Abelson leukemia (ABL1) genes. Current treatment approaches are primarily focused around the use of tyrosine kinase inhibitors (TKIs), such as imatinib, which inhibit the oncogenic potential of the BCR::ABL1 fusion product that is generated as a result of the translocation. Since the approval of imatinib in 2001 by the FDA and EMA, second- and third-generation TKIs have been developed, such as nilotinib, dasatinib and bosutinib, each with varying affinities for different mutations in the kinase domain. Novel drugs continue to be developed; for example, in October 2021, asciminib, an oral, small molecule, selective allosteric inhibitor targeting the myristoyl pocket of the BCR::ABL1 tyrosine kinase, was granted FDA approval for adult patients with Ph+ CML in the chronic phase and a mutation in T315I.
Despite the availability of a large number of TKIs, there remain clinical challenges in the treatment of CML. Roughly half of all TKI treatment discontinuations are a result of TKI toxicity, and intolerance and resistance to TKIs occur frequently. Furthermore, the treatment is not curative as TKI therapy does not eliminate quiescent leukemia stem cells which are not dependent on BCR::ABL1 for survival.
Further research is needed to develop new treatment approaches which can offer improved disease control and reduced toxicity. In addition, finding ways to overcome treatment resistance is crucial to improving long-term survival outcomes. This Research Topic welcomes manuscripts on the following topics:
- Novel targeted agents for the treatment of CML
- Combination approached to the treatment of CML
- Overcoming drug resistance in CML
- Validated biomarkers for monitoring treatment response in CML
- Reducing and managing treatment-related toxicities in CML
Please note: manuscripts that are solely based on bioinformatics or computational analysis of public databases without validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
