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Cooperative genetic changes in pediatric B-cell precursor acute lymphoblastic leukemia with deletions or mutations of IKZF1.

Olsson, Linda LU ; Albitar, Ferras LU ; Castor, Anders LU ; Behrendtz, Mikael; Biloglav, Andrea LU ; Paulsson, Kajsa LU and Johansson, Bertil LU (2015) In Genes, Chromosomes and Cancer 54(5). p.315-325
Abstract
In contrast to IKZF1 deletions (ΔIKZF1), IKZF1 sequence mutations (mutIKZF1) have been reported to be rare in B-cell precursor acute lymphoblastic leukemia and their clinical implications are unknown. We performed targeted deep sequencing of all exons of IKZF1 in 140 pediatric cases, eight (5.7%) of which harbored a mutIKZF1. The probabilities of relapse (pRel) and event-free survival (pEFS) did not differ between cases with or without mutIKZF1, whereas pEFS was decreased and pRel increased in ΔIKZF1-positive case. Coexisting microdeletions, mutations (FLT3, JAK2, SH2B3, and SPRED1), and rearrangements (ABL1, CRLF2, JAK2, and PDGFRB) in 35 ΔIKZF1 and/or mutIKZF1-positive cases were ascertained using fluorescence in situ hybridization,... (More)
In contrast to IKZF1 deletions (ΔIKZF1), IKZF1 sequence mutations (mutIKZF1) have been reported to be rare in B-cell precursor acute lymphoblastic leukemia and their clinical implications are unknown. We performed targeted deep sequencing of all exons of IKZF1 in 140 pediatric cases, eight (5.7%) of which harbored a mutIKZF1. The probabilities of relapse (pRel) and event-free survival (pEFS) did not differ between cases with or without mutIKZF1, whereas pEFS was decreased and pRel increased in ΔIKZF1-positive case. Coexisting microdeletions, mutations (FLT3, JAK2, SH2B3, and SPRED1), and rearrangements (ABL1, CRLF2, JAK2, and PDGFRB) in 35 ΔIKZF1 and/or mutIKZF1-positive cases were ascertained using fluorescence in situ hybridization, single nucleotide polymorphism array, Sanger, and targeted deep sequencing analyses. The overall frequencies of copy number alterations did not differ between cases with our without ΔIKZF1/mutIKZF1. Deletions of HIST1, SH2B3, and the pseudoautosomal region (PAR1), associated with deregulation of CRLF2, were more common in ΔIKZF1-positive cases, whereas PAR1 deletions and JAK2 mutations were overrepresented in the combined ΔIKZF1/mutIKZF1 group. There was no significant impact on pRel of the deletions in ΔIKZF1-positive cases or of JAK2 mutations in cases with ΔIKZF1/mutIKZF1. In contrast, the pRel was higher (P = 0.005) in ΔIKZF1/mutIKZF1-positive cases with PAR1 deletions. © 2015 Wiley Periodicals, Inc. (Less)
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Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
54
issue
5
pages
315 - 325
publisher
John Wiley & Sons
external identifiers
  • pmid:25727050
  • wos:000351680900005
  • scopus:84925356651
ISSN
1045-2257
DOI
10.1002/gcc.22245
language
English
LU publication?
yes
id
1110d61c-d845-41a0-a943-d86179bce1b5 (old id 5265674)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25727050?dopt=Abstract
date added to LUP
2015-04-01 17:28:18
date last changed
2017-08-06 03:10:59
@article{1110d61c-d845-41a0-a943-d86179bce1b5,
  abstract     = {In contrast to IKZF1 deletions (ΔIKZF1), IKZF1 sequence mutations (mutIKZF1) have been reported to be rare in B-cell precursor acute lymphoblastic leukemia and their clinical implications are unknown. We performed targeted deep sequencing of all exons of IKZF1 in 140 pediatric cases, eight (5.7%) of which harbored a mutIKZF1. The probabilities of relapse (pRel) and event-free survival (pEFS) did not differ between cases with or without mutIKZF1, whereas pEFS was decreased and pRel increased in ΔIKZF1-positive case. Coexisting microdeletions, mutations (FLT3, JAK2, SH2B3, and SPRED1), and rearrangements (ABL1, CRLF2, JAK2, and PDGFRB) in 35 ΔIKZF1 and/or mutIKZF1-positive cases were ascertained using fluorescence in situ hybridization, single nucleotide polymorphism array, Sanger, and targeted deep sequencing analyses. The overall frequencies of copy number alterations did not differ between cases with our without ΔIKZF1/mutIKZF1. Deletions of HIST1, SH2B3, and the pseudoautosomal region (PAR1), associated with deregulation of CRLF2, were more common in ΔIKZF1-positive cases, whereas PAR1 deletions and JAK2 mutations were overrepresented in the combined ΔIKZF1/mutIKZF1 group. There was no significant impact on pRel of the deletions in ΔIKZF1-positive cases or of JAK2 mutations in cases with ΔIKZF1/mutIKZF1. In contrast, the pRel was higher (P = 0.005) in ΔIKZF1/mutIKZF1-positive cases with PAR1 deletions. © 2015 Wiley Periodicals, Inc.},
  author       = {Olsson, Linda and Albitar, Ferras and Castor, Anders and Behrendtz, Mikael and Biloglav, Andrea and Paulsson, Kajsa and Johansson, Bertil},
  issn         = {1045-2257},
  language     = {eng},
  number       = {5},
  pages        = {315--325},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {Cooperative genetic changes in pediatric B-cell precursor acute lymphoblastic leukemia with deletions or mutations of IKZF1.},
  url          = {http://dx.doi.org/10.1002/gcc.22245},
  volume       = {54},
  year         = {2015},
}