TY - JOUR
T1 - T(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia
T2 - An international study of 62 patients
AU - Sandahl, Julie Damgaard
AU - Coenen, Eva A.
AU - Forestier, Erik
AU - Harbott, Jochen
AU - Johansson, Bertil
AU - Kerndrup, Gitte
AU - Adachi, Souichi
AU - Auvrignon, Anne
AU - Berna Beverloo, H.
AU - Cayuela, Jean Michel
AU - Chilton, Lucy
AU - Fornerod, Maarten
AU - de Haas, Valérie
AU - Harrison, Christine J.
AU - Inaba, Hiroto
AU - Kaspers, Gertjan J.L.
AU - Liang, Der Cherng
AU - Locatelli, Franco
AU - Masetti, Riccardo
AU - Perot, Christine
AU - Raimondi, Susana C.
AU - Reinhardt, Katarina
AU - Tomizawa, Daisuke
AU - von Neuhoff, Nils
AU - Zecca, Marco
AU - Zwaan, C. Michel
AU - van den Heuvel-Eibrink, Marry M.
AU - Hasle, Henrik
PY - 2014/5/1
Y1 - 2014/5/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84899748622
U2 - 10.3324/haematol.2013.098517
DO - 10.3324/haematol.2013.098517
M3 - Article
C2 - 24441146
AN - SCOPUS:84899748622
SN - 0390-6078
VL - 99
SP - 865
EP - 872
JO - Haematologica
JF - Haematologica
IS - 5
ER -