GENES ASSOCIATED WITH LEUKEMIA AND DOWN SYNDROME: SYSTEMATIC REVIEW STUDY

INTRODUCTION AND OBJECTIVES: Among the genetic alterations, Down syndrome (DS) is the most frequent chromosomal anomaly which can occur in three distinct forms: meiotic nondisjunction, Robertsonian translocation, or mosaicism. The greatest risk factor for this alteration is the advanced age of the parents, especially the maternal. Down's syndrome brings a set of physical characteristics and clinical alterations, such as vision, hearing and thyroid problems, otitis, convulsion, congenital heart disease, in addition to leukemia, which can be acute myeloid (AML) or lymphocytic leukemia (ALL). Leukemia is a form of malignant blood cancer that results from the mutation of white blood cells with a 20% mortality rate in children. Children with DS are 500 times more likely to develop AML, and 20 times for ALL than children without the syndrome. However, there is little evidence about this relationship. Therefore, the objective of the present work was to identify and analyze the main genes involved in the development of leukemia in children with DS, highlighting their relevance and biological effects. MATERIAL AND METHODS: The present work consists of a systematic review of articles published in the last ten years (2012) on the genes involved in the main forms of leukemia observed in children with DS. Scientific articles in Portuguese and English found in the Pubmed and SciELO search platforms were selected, using the following descriptors: Down syndrome and (“childhood leukemia” or “infantile leukemia” or “infant leukemia” or “children leukemia”) and (“gene expression” or “genetics expression”). RESULTS AND CONCLUSION: As preliminary results, eight hundred and twelve articles were found, remaining two hundred after the exclusion of duplicates. Of these two hundred, after exclusion criteria, 12 articles were included in this review, which 5 were cell culture (41.7%), 4 case-control studies (33.3%), 2 cohort and case-control (16.7%) and 1 cohort and cell culture (8.3%). Of the articles included, twenty-one genes had increased expression (GATA1, GATA1s, CRLF2, RUNX1, MYB, CCND2, SKI, HMGN1, PAX5, DYRK1A, LRRC32, USP36, LDLR, RFLNB, MPL, IL3RA, IKZF1, ERG, GATA2, VWF and WT1), and eleven had reduced expression (IRF4, NOTCH1, FLT3, ETS1, MEF2C, HES1, EBF1, IGH, PAX5, DYRK1A and WT1). It is worth noting that the expression of some genes is increased or decreased depending on the type of leukemia. The highlighting of genes pathways, level of expression and functions can be to elucidate gene targets to a better understanding of the genetic factors affecting risk to development leukemia in DS children. Together, these results may be help in the diagnosis, prognosis and treatment individualized of these diseases.