Impact of Genetic Polymorphisms and Biomarkers on the Effectiveness and Toxicity of Treatment of Chronic Myeloid Leukemia and Acute Myeloid Leukemia

Abstract

Most malignant hematological diseases are generally a consequence of acquired mutations or rearrangements in cell replication processes. Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous disease that results from acquired genetic and epigenetic alterations in hematopoietic progenitor cells. Despite the advances made in understanding the pathogenesis of this disease, the overall survival of patients remains very low due to the high relapse rate. Pharmacogenetics and massive sequencing studies have allowed the identification of new recurrent mutations with significant prognostic impact in AML; furthermore, it seems likely that whole genome sequencing will soon become a standard diagnostic test, which will allow the molecular diagnosis of patients. Therefore, it is necessary to develop molecular targets that open new therapeutic perspectives and allow individualized treatment of patients with this aggressive disease. Chronic myeloid leukemia (CML) is the first neoplastic disease for which a characteristic genetic alteration was described. It has, by definition, a genetic marker, the BCR::ABL1 rearrangement, as a consequence of the t9;22(q34;q11) translocation. Its study is essential for the diagnosis of this entity and also for monitoring the response to treatment. Drugs known as tyrosine kinase inhibitors (TKIs) that target the BCR::ABL1 protein (oral targeted therapy) are the conventional treatment of CML, representing a change of paradigm in the management of oncohematological patients.

Molecular Evaluation of the Impact of Polymorphic Variants in Apoptotic (Bcl-2/Bax) and Proinflammatory Cytokine (TNF-α/IL-8) Genes on the Susceptibility and Progression of Myeloproliferative Neoplasms: A Case-Control Biomarker Study

“…In fact, the diagnosis of CML-BC if not presented as a monitored prognosis in CML patients, possesses a substantial challenge in order to be differentiated from AML and might even mimic leukemia with lymphoid origin [88]. It is important to mention that certain genetic abnormalities drive the clonal evolution and blastic transformation of CML and the resulting resistance to TKIs therapy [89,90]. Our report has presented some interesting preliminary findings, which could be further validated in larger cohorts and diverse ethnic populations.…”

Association of genetic predisposition studies in CYP1A1 polymorphism studies in acute myeloid leukemia

“…It is predicted that there are 3.5 new instances per 100,000 people each year, with the rate increasing with age to 12.6 % per 100,000 people among those over the age of 65. Patients are typically between the ages of 60 and 75 when they are first diagnosed, with a median age of 64 years ( Alarcón-Payer et al, 2022 ). The prevalence of AML cases diagnosed in the Saudi population was found to be 17 % and 25 % in male and female population ( Alahmari et al, 2021 ).…”

Constitutional DNA Polymorphisms Associated with the Plasma Imatinib Concentration in Chronic Myeloid Leukemia Patients

“…Although we and others have focused on DNA polymorphisms associated with the response to imatinib [ 13 , 14 , 15 ], very few genetic studies have been performed to explore associations between SNPs and imatinib plasma concentrations [ 16 , 17 , 18 , 19 ], with none in relation to RNA expression. Moreover, the SNP studies were limited to the candidate-gene approach, which has several limitations, such as a reliance on a priori hypotheses and frequent arbitrary choices, which have been largely detailed [ 20 , 21 ].…”