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Klin Padiatr 2013; 225(S 01): S30-S33
DOI: 10.1055/s-0033-1337960
Zum 80. Geburtstag von Prof. Riehm
© Georg Thieme Verlag KG Stuttgart · New York

Cytogenetic Aspects of Childhood Leukemias

Zytogenetische Aspekte bei Leukämien im Kindesalter
F. Lampert
1   Department of General Pediatrics, Hematology and Oncology, Justus Liebig University, Giessen, Germany
,
J. Harbott
1   Department of General Pediatrics, Hematology and Oncology, Justus Liebig University, Giessen, Germany
,
A. Borkhardt
2   Clinic of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich Heine University, Düsseldorf, Germany
› Author Affiliations
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Publication History

Publication Date:
22 May 2013 (online)

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Abstract

Recurrent non-random chromosome abnormalities, including numerical or structural changes such as translocations, inversions, insertions or deletions within the leukemia cell nucleus, have been discovered in approximately 80% of patients with a malignant hematological disease. These reciprocal translocations correlate with specific cellular subtypes of hematopoeisis at the stage of their maturation arrest and are therefore important for diagnosis. Some of these aberrations are independent prognostic indicators and help to stratify patients into different risk-adapted therapy groups. Owing to new laboratory methods such as the fluorescence in situ hybridization (FISH) and modified polymerase chain reaction (RT-PCR) the chromosomal breakpoints can be investigated and the rearrangements of genes which produce the abnormal proteins can be identified. Due to the high sensitivity of these available data a new prognostic factor, the “minimal residual disease” (MRD), can be investigated at diagnosis and at intervals during the treatment period. Since we now know which onkoproteins are involved, a target-directed therapy with inhibitors might be possible in the future.

Standard cytogenetic and molecular genetic analysis of the leukemia karyotype is of the utmost importance for classification (WHO), therapy and therapy results in the acute childhood leukemias.

Zusammenfassung

Erworbene chromosomale Aberrationen nume­rischer oder struktureller Art wie Translokationen, Inversionen, Insertionen oder Deletionen in den Zellkernen der jeweiligen malignen hämatologischen Erkrankung können bei etwa 80% der Patienten nachgewiesen werden. Bei den akuten Leukämien im Kindesalter handelt es sich meist um reziproke Translokationen, die mit bestimmten Zelltypen der Hämatopoese im Zeitpunkt ihrer Ausreifungshemmung korreliert sind. Sie stellen daher bei der Diagnostik der Leukämien eine wichtige Ergänzung dar. Einige dieser Aberrationen sind unabhängige prognostische Faktoren, so dass sie als Indikatoren zur Stratifizierung der Patienten in bestimmte risiko-adaptierte Therapiegruppen eingesetzt werden. Mit Hilfe zusätzlicher Techniken wie Fluoreszenz in situ Hybridisierung (FISH) und Molekulargenetik (RT-PCR, Southern blot) können die chromosomalen Bruchpunkte mit den beteiligten Genverschiebungen (die die abnormen Proteine produzieren) identifiziert werden. Bei der hohen Sensitivität dieser jetzt erhältlichen Daten kann damit auch die „minimale Resterkrankung“ (MRD) bei Diagnose und Verlauf erkannt werden. Auch bieten die nun ­identifizierten Onkoproteine Möglichkeiten einer zielgerichteten Therapie durch entsprechende Inhibitoren.

Die zyto- und molekulargenetische Untersu­chung des Leukämie-Karyotyps ist somit klinisch ganz wichtig für die Klassifizierung (WHO), die Therapie und den Behandlungserfolg bei den Leukämien im Kindesalter.

Key words

cytogenetic analysis - chromosome abnormalities - childhood leukemias - hyperdiploidy - translocations

Schlüsselwörter

cytogenetische Analyse - chromosomale Aberrationen - Leukämien im Kindesalter - Hyperdiploidie - Translokationen
 

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