The Evolving Landscape of Frontline Therapy in Chronic Phase Chronic Myeloid Leukemia (CML)

DNA Adducts in Cancer Chemotherapy

“…Busulfan 30 is a directly alkylating drug approved in 1954. It served as the front-line therapy for managing chronic myeloid leukemia before the approval of the new gold standard drug imatinib (Gleevec) in 2001 . It is still widely used in combination with other chemotherapeutic agents such as cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic cell transplantation. , The well-accepted mechanism of action of busulfan is to form DNA mono- and cross-link adducts via direct alkylation of the two reactive sulfonate groups (Figure ).…”

Activation of ERK1/2 by MOS and TPL2 leads to dasatinib resistance in chronic myeloid leukaemia cells

“…BCR::ABL1 tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib and dasatinib are currently the first‐line agents for the treatment of CML 4 . Compared to conventional interferon therapy, these inhibitors have markedly improved the 5‐year survival rate of chronic phase CML patients to more than 90% 5 . However, approximately 30% of patients who receive BCR::ABL1 TKIs develop resistance or intolerance, which is a major clinical problem 6 …”

“…4 Compared to conventional interferon therapy, these inhibitors have markedly improved the 5-year survival rate of chronic phase CML patients to more than 90%. 5 However, approximately 30% of patients who receive BCR::ABL1 TKIs develop resistance or intolerance, which is a major clinical problem. 6 A cause of BCR::ABL1 TKI resistance is point mutations in the kinase domain within the BCR::ABL1 protein, which interfere with the binding of BCR::ABL1 TKIs to the BCR::ABL1 protein, thereby reducing the sensitivity of the drug.…”

“… 4 Compared to conventional interferon therapy, these inhibitors have markedly improved the 5‐year survival rate of chronic phase CML patients to more than 90%. 5 However, approximately 30% of patients who receive BCR::ABL1 TKIs develop resistance or intolerance, which is a major clinical problem. 6 …”

Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies

“…The most common of these disorders include chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and B-cell non-Hodgkin’s lymphomas (B-cell NHLs) [ 1 , 2 ]. Historically, the mainstays of therapy for these diseases have been chemotherapy, radiotherapy, and bone marrow transplantation (BMT) [ 3 , 4 , 5 , 6 ].…”