Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs: A literature review

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm and was the first neoplastic disease associated with a well-defined genotypic anomaly ― the presence of the Philadelphia chromosome. The advances in cytogenetic and molecular assays are of great importance to the diagnosis, prognosis, treatment, and monitoring of CML. The discovery of the breakpoint cluster region (BCR)-Abelson murine leukemia (ABL) 1 fusion oncogene has revolutionized the treatment of CML patients by allowing the development of targeted drugs that inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein. Tyrosine kinase inhibitors (known as TKIs) are the standard therapy for CML and greatly increase the survival rates, despite adverse effects and the odds of residual disease after discontinuation of treatment. As therapeutic alternatives, the subsequent TKIs lead to faster and deeper molecular remissions; however, with the emergence of resistance to these drugs, immunotherapy appears as an alternative, which may have a cure potential in these patients. Against this background, this article aims at providing an overview on CML clinical management and a summary on the main targeted drugs available in that context.

Integrated Genomic Analysis Identifies ANKRD36 Gene as a Novel and Common Biomarker of Disease Progression in Chronic Myeloid Leukemia

“…Since these cells are immature, they are not fully functional [2]. The excessive proliferation of progenitor cells and blasts results in a change in the balance between regeneration and differentiation [3]. Approximately 15% of all leukemias are CML, which means that 2 out of 100,000 individuals develop CML yearly.…”

Utilizing preclinical models to develop targeted therapies for rare central nervous system cancers

“…For example, in Chronic Myeloid Leukemia (CML), discovery of the BCR-ABL oncoprotein with high tyrosine kinase activity led to the development of Imatinib, a tyrosine kinase inhibitor (TKI), as an extremely successful therapeutic followed by use of second- and third-generation TKIs to treat resistant CML. 82 However, rare tumors caused by these genetic events are difficult to study due to limited tumor tissue samples; furthermore, the oncogenic driver may not be directly targetable. An additional obstacle in developing novel therapeutics for rare cancers are that large, randomized clinical trials are impossible due to the low number of patients.…”

Association between adherence to oral therapies in cancer patients and clinical outcome: A systematic review of the literature

“…The most commonly prominent diseases included in the studies are CML and breast cancer, presumably because of the availability of long‐term oral treatments that offer the researcher a greater amount of data and longer exposure times 51 …”