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Familiäre Leukämien

Familial leukemias

Zusammenfassung

Im Gefolge einer Vielzahl von genetisch bedingten Erkrankungen, wie den DNA-Reparatur-Defizienz-Syndromen, Tumordispositions-, Immundefizienz-, Cancer-Family- und Bone-Marrow-Failure-Syndromen sowie bei einigen angeborenen Chromosomenanomalien werden oft Leukämien und andere hämatologische Neoplasien beobachtet. In letzter Zeit konnten darüber hinaus in Familien mit erhöhter Leukämieinzidenz konstitutionelle Mutationen spezifischer Gene identifiziert werden, die auch bei sporadischen Leukämien in Form von somatischen Mutationen involviert sind. Neben diesen Mutationen mit hoher Penetranz scheinen Genveränderungen mit niedriger Penetranz oder auch Polymorphismen von Genen, die bei der Zellproliferation, der DNA-Reparatur, der Apoptose, der Detoxifizierung u. a. m. eine Rolle spielen, die Disposition zur Leukämieentwicklung bzw. den Krankheitsverlauf zu beeinflussen. Diese neuen Erkenntnisse über konstitutionelle, zu Leukämien disponierende genetische Veränderungen könnten die Kluft zwischen angeborenen und erworbenen genetischen Erkrankungen allmählich überbrücken.

Abstract

Leukemias and other hematological neoplasias are frequently observed in association with different genetic disorders, such as DNA repair deficiency syndromes, tumor predisposition syndromes, immunodeficiency syndromes, familial cancer syndromes and bone marrow failure syndromes, as well as in connection with several constitutional chromosomal anomalies. Recently, in families with increased leukemia incidence, constitutional mutations have been identified in genes that are also affected by somatic mutations in sporadic leukemias. In addition to these high penetrance mutations, gene alterations with low penetrance and polymorphisms seem to predispose to leukemia and/or modify the clinical course of the disease. Predisposing and modifying polymorphisms can be found in genes involved in cell proliferation, apoptosis, DNA repair, detoxification, etc. The novel findings on constitutional genetic alterations predisposing to leukemia start to close the gap between inborn and acquired genetic diseases.

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Correspondence to C. Fonatsch.

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Fonatsch, C., Wimmer , K. Familiäre Leukämien. medgen 19, 197–201 (2007). https://doi.org/10.1007/s11825-007-0014-6

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Schlüsselwörter

  • Leukämie disponierende Syndrome
  • Nichtsyndromal bedingte familiäre Leukämie
  • Konstitutionelle Genmutation
  • Genetischer Polymorphismus
  • Angeboren/erworben

Keywords

  • Leukemia predisposing syndromes
  • Hereditary leukemia without syndromic background
  • Constitutional gene mutations
  • Genetic polymorphisms
  • Congenital/acquired