Abstract: The most common acute leukemia in adults is acute myeloid leukemia (AML). The pathophysiology of the disease associates with cytogenetic abnormalities, gene mutations and aberrant gene expressions. At the molecular level, the disease manifests as changes in both epigenetic and genetic signatures. At the clinical level, two aspects of AML should be taken into account. First, the molecular changes occurring in the disease are important prognostic and predictive markers of AML. Second, use of novel therapies targeting these molecular changes. Currently, cytogenetic abnormalities and molecular alterations are the common biomarkers for the prognosis and choice of treatment for AML. Finding a panel of multiple biomarkers is a crucial diagnostic step for patient classification and serves as a prerequisite for individualized treatment strategies. Furthermore, the most important way of identifying relevant targets for new treatment approaches is defining specific patterns or a spectrum of driver gene mutations occurring in AML. Then, an algorithm can be established by the use of several biomarkers, to be used for personalized medicine. This review deals with molecular alterations, risk stratification, and relevant therapeutic decision-making in AML.


Keywords: acute myeloid leukemia, AML, genetic characterization, risk stratification


Acute Myeloid Leukemia

Acute myeloid leukemia (AML) results from clonal expansion of transformed hematopoietic stem cells (HSCs) through the acquisition of genetic abnormalities including chromosomal rearrangements and multiple gene mutations whereby HSCs are conferred a proliferative and survival advantage and impaired hematopoietic differentiation. AML is a phenotypically and genetically heterogeneous disease. Biologically, different types of mutations which complement each other and cooperate in leukemogenesis should occur in an HSC. Acquired mutations enhance self-renewal and proliferation in an HSC wherein normal mechanisms of differentiation are impaired and eventually lead to a clonal expansion of abnormal immature leukemic blasts which accumulate in the bone marrow. They gradually replace normal hematopoietic tissue and interfere with the production of normal blood cells, resulting in impaired hematopoiesis and bone marrow failure1,2 manifested as cytopenia. Blasts then frequently spread to other parts of the body such as the lymph nodes, spleen, liver, testes and central nervous system.3 Different subtypes of AML are each associated with distinct genetic and molecular abnormalities. Due to heterogeneity in the genomic landscape of leukemia, there are great efforts to devise new-targeted therapies to personalize medicine in AML therapy.4,5


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This is evident by the increasing number of compounds have been made available and combined with conventional chemotherapy during induction or consolidation therapy, novel interventions that are personalized to the host and tumor genotype.6,7

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