Targeting BCR-ABL1-positive leukaemias: a review article

Abstract

Leukaemia describes a mixed group of cancers affecting blood cell development. Its management has changed drastically over the past 40 years and with this we have seen significant improvements in patient outcomes. These advances have come about through continued research into the underpinning mechanisms driving leukaemia development.In addition to better treatments for leukaemia, our understanding of the genes which cause leukaemia has improved. This review focuses on the blood cancer-causing gene BCR::ABL1 which results from an abnormal join between two chromosomes, 9 and 22. The BCR::ABL1 gene most commonly leads to a blood cancer called chronic myeloid leukaemia (CML), but can also cause an acute leukaemia, more commonly Acute Lymphoblastic Leukaemia and rarely, Acute Myeloid Leukaemia.Our knowledge of how the BCR::ABL1 gene and resulting protein drive cancer cell progression and survival through complex processes within the cell which promote cell growth and switch off normal cell death pathways. At the same time, targeted treatments have been developed which directly stop BCR::ABL from affecting cell growth and survival, replacing traditional, more toxic chemotherapy drugs which have a blanket effect on all developing cells, both healthy and cancer cells. These new drugs are called tyrosine kinase inhibitors or "TKIs"; the first of which was designed nearly 25 years ago, and is now called imatinib (trade name "Gleevec" or "Glivec"). TKIs have led to much improved survival for patients, especially with CML, but also reduced toxicity and improved quality of life. Indeed patients with the most benign phase of CML, termed chronic phase, if responding to these targeted drugs, can expect normal life expectancy. This paper will discuss the advances made in BCR::ABL1-positive leukaemias, and discuss ongoing issues with their use and highlight where research must now focus to continue to improve outcomes for patients through precision medicine.

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 ].…”

GL-V9 induce apoptosis of CML cells via MAPK signaling pathway

“…Chronic Myeloid Leukemia (CML) is a type of myeloproliferative neoplasm characterized by excessive production of myeloid cells [ 1 ]. The underlying mechanism of CML is the formation of the t (9; 22) (q34; q11) [ 2 ].…”