Role of Gene Mutations in Acute Myeloid Leukemia: A Review Article

Abstract

Acute myeloid leukemia (AML) is an immensely heterogeneous disease characterized by the clonal growth of promyelocytes or myeloblasts in bone marrow as well as in peripheral blood or tissue.Enhancement in the knowledge of the molecular biology of cancer and recognition of intermittent mutations in AML contribute to favorable circumstances to establish targeted therapies and enhance the clinical outcome. There is high interest in the development of therapies that target definitive abnormalities in AML while eradicating leukemia-initiating cells. In recent years, there has been a better knowledge of the molecular abnormalities that lead to the progression of AML, and the application of new methods in molecular biology techniques has increased that facilitating the advancement of investigational drugs.In this review, literature or information on various gene mutations for AML is discussed. English language articles were scrutinized in plentiful directories or databases like PubMed, Science Direct, Web of Sciences, Google Scholar, and Scopus. The important keywords used for searching databases is “Acute myeloid leukemia”, “Gene mutation in Acute myeloid leukemia”, “Genetic alteration in Acute myeloid leukemia,” and “Genetic abnormalities in Acute myeloid leukemia.”

When inflammatory stressors dramatically change, disease phenotypes may transform between autoimmune hematopoietic failure and myeloid neoplasms

“…Oncogenic mutations in transformed HPCs lead to altered proliferation, self-renewal, and antiapoptotic capacity. The dysregulated growth of leukemic cells results in the overgrowth of their normal counterparts and the suppression of normal blood cell production, clonal hematopoiesis, and corresponding hematological presentations (5)(6)(7)(8). The presence of dysplastic features indicates a diagnosis of MNs, and an increased percentage of myeloblasts is the most significant biomarker representing leukemic hematopoiesis and entry into advanced stages (9,10).…”

“…MDS, MPN, and AML are also highly heterogeneous with somatic mutations involving hundreds of genes in association with their pathogenesis. Each somatic mutation plays a distinctive role in malignant transformation or affects clinical complications, hematological presentations, cellular components, immunological signatures, disease progression, and treatment response (5)(6)(7)(8).…”

“…AA and hMDS are clonal hematological diseases (5,25,27,240). Genetic aberrations in clonal hematopoiesis affect cell proliferation, selfrenewal, and apoptosis (5)(6)(7)(8). While hMDS is an unequivocal MN, AA has a high frequency of transformation to MNs.…”

“…Following the effective treatment of underlying infections, inflammatory stress-mediated antileukemic activities are mitigated, which leads to the simultaneous proliferation of normal and leukemic hematopoieses and transient clinical remission (33-35) due to the prolonged proliferative cycle of damaged HPCs (334-336). Along with an increase in leukemic cell burden due to dysregulated proliferative capacity (5)(6)(7)(8), leukemic cells compromise the hematopoietic pool and outcompete their normal counterparts. Normal hematopoiesis is subsequently suppressed (337-340), which leads to the emergence of symptomatic MNs.…”