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 pre-conception, 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 remains 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 hypothesis 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 occurrence of leukemia requires further investigations. This review summarizes some of the above factors and the direction for future research on the etiology of acute leukemias.

Prevalence of Leukemia Subtype in the Western Area of Libya: A Focus on Tripoli and Sabratha Cities

“…Geographically, the distribution of leukemia burden is patterned by country-level development, with age-standardized incidence, and mortality higher in more developed countries. In this study, some risk factors are not included due to data missed however, many factors may be important to evaluate leukemia occurrence such as exposure chemicals to radiation, chemotherapy, genetic syndromes, and lifestyle factors like smoking [7].…”

“…Moreover, it was found that countries with higher income levels had a higher incidence of 1.5 times higher than low-income countries [6]. GLOBOCAN 2020 estimated that leukemia was the 15th most frequently diagnosed cancer worldwide and it is ranked as the 11th leading cause of cancer-related mortality, accounting for about 4.7% of all cancer-related deaths [4,7]. Pathophysiological, leukemia occurs due to the malignant transformation of pluripotent hematopoietic stem cells (both myeloid and lymphoid precursors).…”

Mycovirus Containing Aspergillus flavus and Acute Lymphoblastic Leukemia: Carcinogenesis beyond Mycotoxin Production

“…Some of the known DNA viruses that are capable of causing human cancers are Epstein-Barr (EB) virus, human papilloma virus, hepatitis B virus, and human herpes virus 8. The relationship of EB virus to the development of Burkitt's lymphoma and nasopharyngeal carcinoma is well established [53][54][55][56][57][58][59]. Likewise, the relation of human papilloma virus and the development of cervical cancer and retention of HPV viral oncoproteins E6 and E7 for their continued expression and proliferation has been demonstrated [60][61][62][63].…”

Rare Association of Tuberous sclerosis with Acute Lymphoblastic Leukemia: Case Report with Review of Literature

“…1 Recent revolution in next-generation sequencing has uncovered many novel somatic mutations and rearrangements in ALL cells, which have prognostic and therapeutic implications. 2,3 Similarly, it has led to recognition of germline variants in the same genes (e.g., PAX5, ETV6, and IKZF1) with somatic mutations commonly associated with ALL (►Table 1). 4,5 Apart from increasing the risk of developing ALL, germline variants may influence diagnostic testing, genetic counseling, and response to antileukemic treatment.…”

“…Down's syndrome, Shwachman's syndrome, Fanconi anemia, Bloom's syndrome, neurofibromatosis, and ataxia telangiectasia are well-recognized conditions associated with ALL. 3 In this report, we describe novel association of T-cell ALL (T-ALL) with tuberous sclerosis (TS), also known as tuberous sclerosis complex (TSC). TSC is autosomal dominant neurocutaneous syndrome characterized by formation of benign hamartoma in various tissues including brain, heart, and kidneys.…”