Chronic Myeloid Leukemia, from Pathophysiology to Treatment-Free Remission: A Narrative Literature Review

Abstract

Chronic myeloid leukemia (CML) is one of the most common leukemias occurring in the adult population. The course of CML is divided into three phases: the chronic phase, the acceleration phase, and the blast phase. Pathophysiology of CML revolves around Philadelphia chromosome that constitutively activate tyrosine kinase through BCR-ABL1 oncoprotein. In the era of tyrosine kinase inhibitors (TKIs), CML patients now have a similar life expectancy to people without CML, and it is now very rare for CML patients to progress to the blast phase. Only a small proportion of CML patients have resistance to TKI, caused by BCR-ABL1 point mutations. CML patients with TKI resistance should be treated with second or third generation TKI, depending on the BCR-ABL1 mutation. Recently, many studies have shown that it is possible for CML patients who achieve a long-term deep molecular response to stop TKIs treatment and maintain remission. This review aimed to provide an overview of CML, including its pathophysiology, clinical manifestations, the role of stem cells, CML treatments, and treatment-free remission.

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

“…Chronic myelogenous leukemia (also known as chronic myeloid leukemia) is a myeloproliferative neoplastic disease characterized by the chromosomal translocation t(9;22)(q34;q11.2), resulting in the presence of the Philadelphia chromosome. The mentioned translocation produces the BCR- ABL1 fusion oncogene, encoding for a constitutively active tyrosine kinase, making leukemia cells sensitive to tyrosine kinase inhibition, with very good 5-year survival rates (90%) [ 237 , 238 , 239 ].…”

Biology and Therapeutic Properties of Mesenchymal Stem Cells in Leukemia

“…The pathophysiology of CML is defined by the BCR-ABL1 fusion oncoprotein. This oncoprotein acts as a constitutively expressed defective tyrosine kinase, affecting downstream pathways involved in cell growth, survival, apoptosis, and transcription factors [ 113 , 114 ]. Despite advancements in TKIs like imatinib, dasatinib, and nilotinib, CML treatment faces challenges due to the persistence of leukemia stem cells (LSCs) and incomplete molecular responses in many patients [ 115 , 116 , 117 ].…”

Mechanisms underlying therapeutic resistance of tyrosine kinase inhibitors in chronic myeloid leukemia

“…BCR-ABL fusion genes are necessary for CML to develop; however, the BCR-ABL oncogene alone is not sufficient to explain disease progression 11 , 12 . In fact, BCR-ABL transcript levels increase with disease progression, promoting a secondary molecular, chromosomal-level hit and ultimately leading to the expansion of malignant cell clones 13 .…”