Genes and childhood leukemia.
Leukemia is a heterogeneous hematologic malignancy originating from a multipotent hematopoietic stem cell. It ranks among the commonest cancers in childhood and is characterized by excessive proliferation and differentiation block. The process of leukemogenesis is governed by genetic changes at both the cytogenetic and molecular level. According to numerous analyses, a large spectrum of mutations and rearrangements underlying the disease affect essential cellular transduction pathways, genes ensuring proper course of hematopoiesis, oncogenes, tumor suppressors and apoptosis regulators. Common lesions include translocations to T cell receptor (TCR) loci in T-lineage acute lymphoblastic leukemia (T-ALL), mutations of transcription factors regulating B-lineage development and cell maturation in B-lineage acute lymphoblastic leukemia (B-ALL) (PAX5, TCF3, EBF1, etc.), aberrational disruption of genes coding for transcription factors and coactivators in acute myeloid leukemia (AML) (e.g. CBF) or BCR-ABL1 fusion and activation of multiple kinases in chronic myeloid leukemia (CML). These alterations severely impair cell function. Broadening knowledge of the genetic background gives an insight into the pathobiology of a disease and allows for a better understanding of it. An appropriate investigation of genomic events yields diagnostic, prognostic and therapeutic implications. Broadening knowledge of the pathogenesis of leukemia seems to be a promising contribution to precise stratification of patients, reducing the toxicity and adverse effects caused by medical intervention, treatment personalization and introduction of targeted therapy accessible to a wide range of patients.
Medical Biotechnology Student at Poznan University of Medical Sciences.
Julita
J
Kęsy
Department of Paediatric Oncology, Haematology and Transplantology, Poznan University of Medical Sciences.
Danuta
D
Januszkiewicz-Lewandowska
D000293:Adolescent; D002454:Cell Differentiation / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D009154:Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics*
D014157:Transcription Factors