Evolution of CML treatment

Excerpt

Chronic myeloid leukemia (CML) is a hematopoietic malignancy caused by the Philadelphia chromosome, which is formed by reciprocal translocation of chromosomes 9 and 22. The prognosis for CML patients has improved dramatically since the introduction of imatinib mesylate, an ATP competitive type tyrosine kinase inhibitor (TKI), in 2001. However, approximately one-third of CML patients become resistant and/or intolerant to imatinib mesylate. To overcome this, second-generation TKIs dasatinib, nilotinib, and bosutinib were developed. These second-generation TKIs cause faster and deeper remission, and all three are now available as a first-line treatment. However, these TKIs are ineffective against the T315I mutation. Thus, a third-generation TKI, ponatinib, was developed. Use of these five TKIs means that the life-expectancy of CML patients is almost the same as that of healthy individuals [1]. Furthermore, many clinical trials show that a certain number of CML patients do not develop molecular relapse, even after discontinuing TKIs [2]. CML is a hematological malignancy that benefits from the most advanced treatments; therefore, the knowledge gained from studying CML is extremely useful not only in the context of other hematological malignancies but also in the context of other cancers. …