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t(6;9)(p22; q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients

Sandahl, Julie Damgaard; Coenen, Eva A.; Forestier, Erik; Harbott, Jochen; Johansson, Bertil LU ; Kerndrup, Gitte; Adachi, Souichi; Auvrignon, Anne; Beverloo, H. Berna and Cayuela, Jean-Michel, et al. (2014) In Haematologica 99(5). p.865-872
Abstract
Acute myeloid leukemia with t(6; 9)(p22; q34) is listed as a distinct entity in the 2008 World Health Organization classification, but little is known about the clinical implications of t(6; 9)-positive myeloid leukemia in children. This international multicenter study presents the clinical and genetic characteristics of 62 pediatric patients with t(6; 9)/DEKNUP214-rearranged myeloid leukemia; 54 diagnosed as having acute myeloid leukemia, representing <1% of all childhood acute myeloid leukemia, and eight as having myelodysplastic syndrome. The t(6; 9)/DEK-NUP214 was associated with relatively late onset (median age 10.4 years), male predominance (sex ratio 1.7), French-American-British M2 classification (54%), myelodysplasia (100%),... (More)
Acute myeloid leukemia with t(6; 9)(p22; q34) is listed as a distinct entity in the 2008 World Health Organization classification, but little is known about the clinical implications of t(6; 9)-positive myeloid leukemia in children. This international multicenter study presents the clinical and genetic characteristics of 62 pediatric patients with t(6; 9)/DEKNUP214-rearranged myeloid leukemia; 54 diagnosed as having acute myeloid leukemia, representing <1% of all childhood acute myeloid leukemia, and eight as having myelodysplastic syndrome. The t(6; 9)/DEK-NUP214 was associated with relatively late onset (median age 10.4 years), male predominance (sex ratio 1.7), French-American-British M2 classification (54%), myelodysplasia (100%), and FLT3-ITD (42%). Outcome was substantially better than previously reported with a 5-year event-free survival of 32%, 5-year overall survival of 53%, and a 5-year cumulative incidence of relapse of 57%. Hematopoietic stem cell transplantation in first complete remission improved the 5-year event-free survival compared with chemotherapy alone (68% versus 18%; P<0.01) but not the overall survival (68% versus 54%; P=0.48). The presence of FLT3-ITD had a non-significant negative effect on 5-year overall survival compared with non-mutated cases (22% versus 62%; P=0.13). Gene expression profiling showed a unique signature characterized by significantly higher expression of EYA3, SESN1, PRDM2/RIZ, and HIST2H4 genes. In conclusion, t(6; 9)/DEK-NUP214 represents a unique subtype of acute myeloid leukemia with a high risk of relapse, high frequency of FLT3-ITD, and a specific gene expression signature. (Less)
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type
Contribution to journal
publication status
published
subject
in
Haematologica
volume
99
issue
5
pages
865 - 872
publisher
Ferrata Storti Foundation
external identifiers
  • wos:000336257500014
  • scopus:84899748622
ISSN
1592-8721
DOI
10.3324/haematol.2013.098517
language
English
LU publication?
yes
id
6f39d8c9-d961-4f09-adcc-d00f1115d469 (old id 4559120)
date added to LUP
2014-08-01 07:42:46
date last changed
2017-11-12 03:33:31
@article{6f39d8c9-d961-4f09-adcc-d00f1115d469,
  abstract     = {Acute myeloid leukemia with t(6; 9)(p22; q34) is listed as a distinct entity in the 2008 World Health Organization classification, but little is known about the clinical implications of t(6; 9)-positive myeloid leukemia in children. This international multicenter study presents the clinical and genetic characteristics of 62 pediatric patients with t(6; 9)/DEKNUP214-rearranged myeloid leukemia; 54 diagnosed as having acute myeloid leukemia, representing &lt;1% of all childhood acute myeloid leukemia, and eight as having myelodysplastic syndrome. The t(6; 9)/DEK-NUP214 was associated with relatively late onset (median age 10.4 years), male predominance (sex ratio 1.7), French-American-British M2 classification (54%), myelodysplasia (100%), and FLT3-ITD (42%). Outcome was substantially better than previously reported with a 5-year event-free survival of 32%, 5-year overall survival of 53%, and a 5-year cumulative incidence of relapse of 57%. Hematopoietic stem cell transplantation in first complete remission improved the 5-year event-free survival compared with chemotherapy alone (68% versus 18%; P&lt;0.01) but not the overall survival (68% versus 54%; P=0.48). The presence of FLT3-ITD had a non-significant negative effect on 5-year overall survival compared with non-mutated cases (22% versus 62%; P=0.13). Gene expression profiling showed a unique signature characterized by significantly higher expression of EYA3, SESN1, PRDM2/RIZ, and HIST2H4 genes. In conclusion, t(6; 9)/DEK-NUP214 represents a unique subtype of acute myeloid leukemia with a high risk of relapse, high frequency of FLT3-ITD, and a specific gene expression signature.},
  author       = {Sandahl, Julie Damgaard and Coenen, Eva A. and Forestier, Erik and Harbott, Jochen and Johansson, Bertil and Kerndrup, Gitte and Adachi, Souichi and Auvrignon, Anne and Beverloo, H. Berna and Cayuela, Jean-Michel and Chilton, Lucy and Fornerod, Maarten and de Haas, Valerie and Harrison, Christine J. and Inaba, Hiroto and Kaspers, Gertjan J. L. and Liang, Der-Cherng and Locatelli, Franco and Masetti, Riccardo and Perot, Christine and Raimondi, Susana C. and Reinhardt, Katarina and Tomizawa, Daisuke and von Neuhoff, Nils and Zecca, Marco and Zwaan, C. Michel and van den Heuvel-Eibrink, Marry M. and Hasle, Henrik},
  issn         = {1592-8721},
  language     = {eng},
  number       = {5},
  pages        = {865--872},
  publisher    = {Ferrata Storti Foundation},
  series       = {Haematologica},
  title        = {t(6;9)(p22; q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients},
  url          = {http://dx.doi.org/10.3324/haematol.2013.098517},
  volume       = {99},
  year         = {2014},
}