title: Chromosomal aberrations in congenital bone marrow failure disorders--an early indicator for leukemogenesis?
abstract: As chromosomal instability may contribute to leukemogenesis in patients with congenital bone marrow failure (CBMF) disorders, it was the aim of this study to characterize chromosomally aberrant clones that arise during the clinical course of disease by means of R-banding and fluorescence in situ hybridization (FISH) analyses. In addition, multicolor-FISH and array-comparative genomic hybridization (CGH) were applied to characterize clonal chromosome aberrations in more detail. Between January 2004 and December 2005, we prospectively analyzed 90 samples of 73 patients with proven or suspected CBMF disorders enrolled in a German Study Network of CBMF diseases. Clonal aberrations could be identified in four of 73 patients examined. In one child with congenital thrombocytopenia, Jacobsen syndrome [del(11)(q24)c] was diagnosed, and thus a CBMF could be excluded. In a girl with Shwachman-Diamond syndrome, two independent clones, one with an isochromosome i(7)(q10), another with a complex aberrant karyotype, were identified. Simultaneously, transition into a myelodysplastic syndrome (MDS) occurred. The brother, who was also afflicted with Shwachman-Diamond syndrome, showed an isochromosome i(7q) as a single aberration. In the fourth patient with severe congenital neutropenia, an add(21)(q22) marker containing a low-level amplification of the AML1 gene was identified at the time point of transition into acute myelogenous leukemia (AML). In summary, we suggest that follow-up of patients with CBMF using chromosome and FISH analyses will be helpful for the early detection of transition into MDS or AML and thus should be an integral part of the clinical management of these patients.
authors.affiliation: Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany. goehring.gudrun@mh-hannover.de
authors.forename: G
authors.initials: G
authors.lastname: Göhring
authors.forename: A
authors.initials: A
authors.lastname: Karow
authors.forename: D
authors.initials: D
authors.lastname: Steinemann
authors.forename: L
authors.initials: L
authors.lastname: Wilkens
authors.forename: P
authors.initials: P
authors.lastname: Lichter
authors.forename: C
authors.initials: C
authors.lastname: Zeidler
authors.forename: C
authors.initials: C
authors.lastname: Niemeyer
authors.forename: K
authors.initials: K
authors.lastname: Welte
authors.forename: B
authors.initials: B
authors.lastname: Schlegelberger
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D043171:Chromosomal Instability; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D054868:Jacobsen Distal 11q Deletion Syndrome / Q000150:complications / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000151:congenital / Q000235:genetics*; D009503:Neutropenia / Q000150:complications / Q000151:congenital / Q000235:genetics*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human