title: Role of chromosomal aberrations in clonal diversity and progression of acute myeloid leukemia.
abstract: Genetic abnormalities are a hallmark of cancer. Hereby, cytogenetic aberrations and small-scale abnormalities, such as single-nucleotide variations and insertion/deletion mutations, have emerged as two alternative modes of genetic diversification. Both mechanisms are at work in acute myeloid leukemia (AML), in which conventional karyotyping and molecular studies demonstrate that gene mutations occur predominantly in cytogenetically normal AML, whereas chromosomal changes are a driving force of development and progression of disease in aberrant karyotype AML. All steps of disease evolution in AML, ranging from the transformation of preleukemic clones into overt leukemia to the expansion and recurrence of malignant clones, are paralleled by clonal evolution at either the gene mutation or chromosome aberration level. Preleukemic conditions, such as Fanconi anemia and Bloom syndrome, demonstrate that the acquisition of chromosomal aberrations can contribute to leukemic transformation. Similar to what has been shown at the mutational level, expansion and recurrence of AML clones goes along with increasing genetic diversification. Hereby, cytogenetically more evolved subclones are at a proliferative advantage and outgrow ancestor clones or have evolved toward a more aggressive behavior with additional newly acquired aberrations as compared with the initial leukemic clone, respectively.
authors: 1] Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany [2] Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors: T
authors: T
authors: Bochtler
authors: Department of Translational Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: S
authors: S
authors: Fröhling
authors: 1] Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany [2] Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors: A
authors: A
authors: Krämer
mesh_terms: D002869:Chromosome Aberrations; D002999:Clone Cells; D014644:Genetic Variation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D011379:Prognosis