Abstract
Normal karyotype (NK) is the most common cytogenetic group in acute myeloid leukemia
(AML) diagnosis; however, up to 50% of these patients at relapse will have aberrant
karyotype (AK) AML. To determine the etiology of relapsed AK AML cells, we evaluated
cytogenetic, immunophenotypic, and molecular results of 17 patients with diagnostic
NK AML and relapsed AK AML at our institute. AK AML karyotype was diverse, involving
no favorable and largely (8 of 17) complex cytogenetics. Despite clear cytogenetic
differences, immunophenotype and NPM1/FLT3 gene mutation status did not change between presentation and relapse in 83% (10 of
12) and 94% (15 of 16) cases, respectively. High-resolution array-based comparative
genomic hybridization (aCGH) performed via paired aCGH on NK AML and AK AML samples
from the same patient confirmed cytogenetic aberrations only in the relapse sample.
Analysis of 16 additional diagnostic NK AML samples revealed no evidence of submicroscopic
aberrations undetected by conventional cytogenetics in any case. These results favor
evolution of NK AML leukemia cells with acquisition of novel genetic changes as the
most common etiology of AK AML relapse as opposed to secondary leukemogenesis. Additional
studies are needed to confirm whether AK AML cells represent selection of rare preexisting
clones below aCGH detection and to further characterize the molecular lesions found
at time of AK AML relapse.
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Article info
Publication history
Accepted:
July 2,
2010
Received in revised form:
June 28,
2010
Received:
February 23,
2010
Identification
Copyright
© 2010 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
