Etiology of Acute Leukemia: A Review

SIMPLE SUMMARY: Acute leukemias are some of the most common cancers affecting all age groups. Despite a significant improvement made in the treatment of acute leukemias, their cause remains unknown. A number of genetic and environmental factors for the development of acute leukemias have been proposed, but none have been proven. Undoubtedly, genetics have a major role in the development of these diseases. The effects of a variety of environmental factors, occupations and hobbies have been explored. A recent “two-hit” theory” for the development of acute lymphoblastic leukemia has been proposed. This combines genetic factors and exposure to infections for the development of this disease. Several genetic factors are suggested. Most recently, for the infection portion, exposure to a virus containing Aspergillus Flavus has been proposed. This review summarizes what is currently known about the factors that are proposed for the development of acute leukemias. 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.