t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients.
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)/DEK-NUP214-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.
hasle@dadlnet.dk.
Julie Damgaard
JD
Sandahl
Eva A
EA
Coenen
Erik
E
Forestier
Jochen
J
Harbott
Bertil
B
Johansson
Gitte
G
Kerndrup
Souichi
S
Adachi
Anne
A
Auvrignon
H Berna
HB
Beverloo
Jean-Michel
JM
Cayuela
Lucy
L
Chilton
Maarten
M
Fornerod
Valérie
V
de Haas
Christine J
CJ
Harrison
Hiroto
H
Inaba
Gertjan J L
GJ
Kaspers
Der-Cherng
DC
Liang
Franco
F
Locatelli
Riccardo
R
Masetti
Christine
C
Perot
Susana C
SC
Raimondi
Katarina
K
Reinhardt
Daisuke
D
Tomizawa
Nils
N
von Neuhoff
Marco
M
Zecca
C Michel
CM
Zwaan
Marry M
MM
van den Heuvel-Eibrink
Henrik
H
Hasle
D000293:Adolescent; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6; D002899:Chromosomes, Human, Pair 9; D005260:Female; D020869:Gene Expression Profiling; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000628:therapy; D008297:Male; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000628:therapy; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D012008:Recurrence; D014178:Translocation, Genetic; D016896:Treatment Outcome
D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; C085914:NUP214 protein, human; D028861:Nuclear Pore Complex Proteins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D000075223:Poly-ADP-Ribose Binding Proteins