Am J Blood Res 2013;3(2):165-173
Original Article
Refinement of IKZF1 recombination hotspots in pediatric BCP-ALL patients
Claus Meyer, Udo zur Stadt, Gabriele Escherich, Julia Hofmann, Renata Binato, Thayana da Conceição Barbosa, Mariana
Emerenciano, Maria S Pombo-de-Oliveira, Martin Horstmann, Rolf Marschalek
Institute of Pharmaceutical Biology/ZAFES, Goethe-University of Frankfurt, Biocenter, Max-von-Laue-Str. 9, D-60438
Frankfurt/Main, Germany; Center for Diagnostic, University Medical Center Hamburg Eppendorf, Martinistr. 52, Hamburg,
Germany; University Medical Center Hamburg Eppendorf, Clinic of Pediatric Hematology/Oncology, Hamburg, Germany; Bone
Marrow Transplantation Unit, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil; Pediatric Hematology-Oncology
Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil; Childhood Cancer Research Institute and
Clinic of Pediatric Hematology and Oncology, UKE, University of Hamburg, Hamburg, Germany.
Received March 19, 2013; Accepted April 21, 2013; Epub May 5, 2013; Published May 15, 2013
Abstract: Chromosomal translocations resulting in chimeric fusion genes are prototypic for pediatric leukemia patients. The
most known fusions are ETV6-RUNX1 or BCR-ABL1 in B-cell progenitor (BCP)-ALL, and rearrangements of MLL in pediatric
ALL and AML. Genome-wide sequencing projects have revealed additional, recurrent gene mutations in B cell malignancies.
One of these mutations comprises the IKZF1 gene, encoding the IKAROS transcription factor which is one of the essential
transcription factors driving lymphoid development. IKZF1 deletions were first identified by SNP arrays in ALL patients, and
later identified with a high prevalence in BCR-ABL1+ patients. IKZF1 deletions turned out to be an independent prognostic
marker associated with a poor outcome. Here, we characterized IKZF1 deletions in pediatric BCP-ALL patients by combining
MLPA mapping experiments with long distance inverse PCR. The aim of our study was also to compare existing methods with
our approach. Our attempt confirmed many of the existing data but revealed a more complex pattern of recombination sites,
including a total of 4 recombination hotspots. This extended knowledge was translated into a novel, multiplex PCR assay that
allows to perform IKZF1 deletion analyses by using a 2-tube PCR approach. (AJBR1303004).
Keywords: Childhood leukemia, cancer genetics, gene deletion, IKAROS, IKZF1, leukemia markers
Address correspondence to: Dr. Rolf Marschalek, Institute of Pharmaceutical Biology/ZAFES, University of Frankfurt,
Max-von-Laue-Str. 9, 60438 Frankfurt/Main, Germany. Phone: +49-69-798-29647; Fax: +49-69-798-29662; E-mail:
Rolf.Marschalek@em.uni-frankfurt.de
Original Article
Refinement of IKZF1 recombination hotspots in pediatric BCP-ALL patients
Claus Meyer, Udo zur Stadt, Gabriele Escherich, Julia Hofmann, Renata Binato, Thayana da Conceição Barbosa, Mariana
Emerenciano, Maria S Pombo-de-Oliveira, Martin Horstmann, Rolf Marschalek
Institute of Pharmaceutical Biology/ZAFES, Goethe-University of Frankfurt, Biocenter, Max-von-Laue-Str. 9, D-60438
Frankfurt/Main, Germany; Center for Diagnostic, University Medical Center Hamburg Eppendorf, Martinistr. 52, Hamburg,
Germany; University Medical Center Hamburg Eppendorf, Clinic of Pediatric Hematology/Oncology, Hamburg, Germany; Bone
Marrow Transplantation Unit, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil; Pediatric Hematology-Oncology
Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil; Childhood Cancer Research Institute and
Clinic of Pediatric Hematology and Oncology, UKE, University of Hamburg, Hamburg, Germany.
Received March 19, 2013; Accepted April 21, 2013; Epub May 5, 2013; Published May 15, 2013
Abstract: Chromosomal translocations resulting in chimeric fusion genes are prototypic for pediatric leukemia patients. The
most known fusions are ETV6-RUNX1 or BCR-ABL1 in B-cell progenitor (BCP)-ALL, and rearrangements of MLL in pediatric
ALL and AML. Genome-wide sequencing projects have revealed additional, recurrent gene mutations in B cell malignancies.
One of these mutations comprises the IKZF1 gene, encoding the IKAROS transcription factor which is one of the essential
transcription factors driving lymphoid development. IKZF1 deletions were first identified by SNP arrays in ALL patients, and
later identified with a high prevalence in BCR-ABL1+ patients. IKZF1 deletions turned out to be an independent prognostic
marker associated with a poor outcome. Here, we characterized IKZF1 deletions in pediatric BCP-ALL patients by combining
MLPA mapping experiments with long distance inverse PCR. The aim of our study was also to compare existing methods with
our approach. Our attempt confirmed many of the existing data but revealed a more complex pattern of recombination sites,
including a total of 4 recombination hotspots. This extended knowledge was translated into a novel, multiplex PCR assay that
allows to perform IKZF1 deletion analyses by using a 2-tube PCR approach. (AJBR1303004).
Keywords: Childhood leukemia, cancer genetics, gene deletion, IKAROS, IKZF1, leukemia markers
Address correspondence to: Dr. Rolf Marschalek, Institute of Pharmaceutical Biology/ZAFES, University of Frankfurt,
Max-von-Laue-Str. 9, 60438 Frankfurt/Main, Germany. Phone: +49-69-798-29647; Fax: +49-69-798-29662; E-mail:
Rolf.Marschalek@em.uni-frankfurt.de
| AJBR Copyright © 2011-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711, USA |
 |  |  |  |  |  |  |