PMID- 17653548
OWN - NLM
STAT- MEDLINE
DCOM- 20080129
LR  - 20070823
IS  - 1432-0584 (Electronic)
IS  - 0939-5555 (Linking)
VI  - 86
IP  - 10
DP  - 2007 Oct
TI  - Chromosomal aberrations in congenital bone marrow failure disorders--an early 
      indicator for leukemogenesis?
PG  - 733-9
AB  - 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.
FAU - Gohring, G
AU  - Gohring G
AD  - Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, 
      Germany. goehring.gudrun@mh-hannover.de
FAU - Karow, A
AU  - Karow A
FAU - Steinemann, D
AU  - Steinemann D
FAU - Wilkens, L
AU  - Wilkens L
FAU - Lichter, P
AU  - Lichter P
FAU - Zeidler, C
AU  - Zeidler C
FAU - Niemeyer, C
AU  - Niemeyer C
FAU - Welte, K
AU  - Welte K
FAU - Schlegelberger, B
AU  - Schlegelberger B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070725
PL  - Germany
TA  - Ann Hematol
JT  - Annals of hematology
JID - 9107334
RN  - 0 (Core Binding Factor Alpha 2 Subunit)
RN  - 0 (RUNX1 protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Case-Control Studies
MH  - Cell Transformation, Neoplastic/genetics
MH  - Child
MH  - Child, Preschool
MH  - Chromosomal Instability
MH  - *Chromosome Aberrations
MH  - Chromosomes, Human/genetics
MH  - Core Binding Factor Alpha 2 Subunit/*genetics
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Infant, Newborn
MH  - Jacobsen Distal 11q Deletion Syndrome/complications/*genetics
MH  - Leukemia, Myeloid, Acute/etiology/*genetics
MH  - Male
MH  - Middle Aged
MH  - Myelodysplastic Syndromes/complications/congenital/*genetics
MH  - Neutropenia/complications/congenital/*genetics
EDAT- 2007/07/27 09:00
MHDA- 2008/01/30 09:00
CRDT- 2007/07/27 09:00
PHST- 2007/04/12 00:00 [received]
PHST- 2007/06/15 00:00 [accepted]
PHST- 2007/07/27 09:00 [pubmed]
PHST- 2008/01/30 09:00 [medline]
PHST- 2007/07/27 09:00 [entrez]
AID - 10.1007/s00277-007-0337-z [doi]
PST - ppublish
SO  - Ann Hematol. 2007 Oct;86(10):733-9. doi: 10.1007/s00277-007-0337-z. Epub 2007 Jul 
      25.