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Blood, 1 April 2002, Vol. 99, No. 7, pp. 2526-2531
NEOPLASIA
A cryptic t(5;11)(q35;p15.5) in 2 children with acute myeloid
leukemia with apparently normal karyotypes, identified by a
multiplex fluorescence in situ hybridization telomere
assay
Jill Brown,
Mays Jawad,
Stephen R. F. Twigg,
Kaan Saracoglu,
Axel Sauerbrey,
Angela E. Thomas,
Roland Eils,
Jochen Harbott, and
Lyndal Kearney
From the Weatherall Institute of Molecular Medicine,
John Radcliffe Hospital, Oxford, United Kingdom; the Department
Intelligent Bioinformatics Systems, Deutsches Krebsforschungszentrum,
Heidelberg, Germany; the Department of Pediatrics, University of Jena,
Germany; the Haematology Department, Royal Hospital for Sick Children,
Edinburgh, United Kingdom; the Oncogenetic Laboratory, Children's
University Hospital, Giessen, Germany; and the Leukaemia Research Fund
Centre, Institute of Cancer Research, Chester Beatty Laboratories,
London, United Kingdom.
The identification of specific chromosome abnormalities in acute
myeloid leukemia (AML) is important for the stratification of patients
into the appropriate treatment protocols. However, a significant
proportion of diagnostic bone marrow karyotypes in AML is reported as
normal by conventional cytogenetic analysis and it is suspected
that these karyotypes may conceal the presence of diagnostically
significant chromosome rearrangements. To address this question, we
have developed a novel 12-color fluorescence in situ hybridization
(FISH) assay for telomeric rearrangements (termed M-TEL), which uses an
optimized set of chromosome-specific subtelomeric probes.
We report here the application of the M-TEL assay to 69 AML cases with
apparently normal karyotypes or an isolated trisomy. Of the 69 cases
examined, 3 abnormalities were identified, all in the normal
karyotype group. The first was a t(11;19)(q23;p13), identified in an
infant with AML-M4. In 2 other young patients with AML (< 19 years),
an apparently identical t(5;11)(q35;p15.5) was identified. Breakpoint
mapping by FISH and reverse transcriptase polymerase chain reaction
(RT-PCR) analysis confirmed that this was the same t(5;11) as
previously identified in 3 children with AML, associated with del(5q)
and resulting in the NUP98-NSD1 gene fusion. The t(5;11)
was not detected by 24-color karyotyping using multiplex FISH (M-FISH),
emphasizing the value of screening with subtelomeric probes for subtle
translocations. This is the first report of the t(5;11)(q35;p15.5) in
association with an apparently normal karyotype, and highlights this as
a new, potentially clinically significant chromosome rearrangement in
childhood AML.
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