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

Genes, Chromosomes & Cancer
L OlssonBertil Johansson

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 deleti...Continue Reading

References

Jan 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·C A KlugI L Weissman
Dec 10, 1998·Nature Structural Biology·M Vignali, J L Workman
May 14, 1999·Current Opinion in Immunology·M CortesK Georgopoulos
Mar 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kimberly J PayneGay M Crooks
Mar 9, 2007·Nature·Charles G MullighanJames R Downing
Apr 15, 2008·Nature·Charles G MullighanJames R Downing
Jan 9, 2009·The New England Journal of Medicine·Charles G MullighanUNKNOWN Children's Oncology Group
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
May 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·Charles G MullighanCheryl L Willman
Sep 23, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Giovanni MartinelliRobin Foà
Dec 17, 2009·Leukemia·K SchmiegelowUNKNOWN Nordic Society of Paediatric Haematology and Oncology
Jan 12, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ching-Hon PuiRobert J Arceci
Jul 10, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Brent W WestonCharles G Mullighan
Aug 3, 2013·Blood·Arianne Perez-GarciaAdolfo A Ferrando
Sep 11, 2014·The New England Journal of Medicine·Kathryn G RobertsCharles G Mullighan

❮ Previous
Next ❯

Citations

Mar 11, 2015·British Journal of Haematology·Linda Olsson, Bertil Johansson
Mar 3, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Martin StanullaUNKNOWN International BFM Study Group
Nov 30, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jian-Feng LiJin-Yan Huang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.