Role of chromosomal aberrations in clonal diversity and progression of acute myeloid leukemia

• Verfasst von: Bochtler, Tilmann [VerfasserIn]
• Verfasst von: Fröhling, Stefan [VerfasserIn]
• Verfasst von: Krämer, Alwin [VerfasserIn]
• Titel: Role of chromosomal aberrations in clonal diversity and progression of acute myeloid leukemia
• Verf.angabe: T Bochtler, S Fröhling and A Krämer
• E-Jahr: 2015
• Jahr: 10 March 2015
• Umfang: 10 S.
• Fussnoten: Gesehen am 06.04.2017
• Titel Quelle: Enthalten in: Leukemia
• Ort Quelle: London : Springer Nature, 1997
• Jahr Quelle: 2015
• Band/Heft Quelle: 29(2015), 6, Seite 1243-1252
• ISSN Quelle: 1476-5551
• DOI: doi:10.1038/leu.2015.32
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1556378920

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.