Etiology of Acute Leukemia: A Review

Abstract

Acute leukemias constitute some of the most common malignant disorders. Despite significant progress made in the treatment of these disorders, their etiology remains unknown. A large and diverse group of genetic and environmental variables have been proposed. The role of a variety of factors, including pre-existing and acquired genetic mutations, exposure to radiation and various chemicals during preconception, pregnancy and throughout life, have been explored. The effects of inherited genetic variations and disorders, pre-existing diseases, infectious agents, hobbies, occupations, prior treatments, and a host of other factors have been proposed, but none is universally applicable to all cases. Variation in the incidence and prognosis based on the age, sex, race, type of the disease, geographic area of residence and other factors are intriguing but remain unexplained. Advances in genomic profiling, including genome-wide gene expression, DNA copy number and single nucleotide polymorphism (SNP) genotype, may shed some light on the role of genetics in these disparities. Separate two-hit hypotheses for the development of acute myeloblastic and lymphoblastic leukemia have been proposed. The latter combines genetics and infection factors resulting in leukemogenesis. A number of pre- and post-natal environmental conditions and exposure to infections, including a mycovirus infected Aspergillus flavus, have been suggested. The exact nature, timing, sequence of the events and mechanisms resulting in the occurrence of leukemia requires further investigations. This review summarizes some of the above factors in acute lymphoblastic and myeloblastic leukemias and the direction for future research on the etiology of these disorders.

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“…Leukemia is a cancer that is present worldwide and affects people of all ages, although predominantly in childhood. In 2018, nearly 430,000 people were diagnosed with any type of leukemia, which accounted for 300,000 deaths around the world [ 13 , 14 ].…”

“…All these drugs present significant side effects, in some cases multidrug resistance, and in the case of etoposide or methotrexate secondary leukemia may develop. In an effort to improve cancer therapy, it was proposed to employ secondary metabolites isolated out of Asteraceae plants for developing new treatments against malignancies, including non-solid tumors such as leukemias [ 8 , 13 , 14 , 15 , 16 ].…”

Green Metallic Nanoparticles for Cancer Therapy: Evaluation Models and Cancer Applications

“…Leukemia includes cancers characterized by disorders of malignant bone marrow cells that promote replacement with immature and undifferentiated abnormal hematopoietic cells so that they do not remove necessary cells, such as red blood cells, healthy platelets, and mature white blood cells (leukocytes), etc. [ 332 ]. Four main subtypes of leukemia are known: chronic lymphoid leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoid leukemia (ALL), and acute myeloid leukemia (AML).…”

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“…Acute leukemias are malignant clonal disorders of the hematopoietic system. Acute leukemias are marked by the diffuse replacement of bone marrow with abnormal immature and undifferentiated hematopoietic cells, resulting in reduced numbers of erythrocytes and platelets in the peripheral blood [ 3 ].…”

“…Chronic leukemias encompass a broad spectrum of diseases characterized by uncontrolled proliferation and expansion of mature, differentiated cells of the hematopoietic system [ 3 ].…”