Activating mutations in human acute megakaryoblastic leukemia.
Oncogenic activation of tyrosine kinase signaling pathway is recurrent in human leukemia. To gain insight into the oncogenic process leading to acute megakaryoblastic leukemia (AMKL), we performed sequence analyses of a subset of oncogenes known to be activated in human myeloid and myeloproliferative disorders. In a series of human AMKL samples from both Down syndrome and non-Down syndrome patients, mutations were identified within KIT, FLT3, JAK2, JAK3, and MPL genes, with a higher frequency in DS than in non-DS patients. The novel mutations were analyzed using BaF3 cells, showing that JAK3 mutations were activating mutations. Finally, we report a novel constitutively active MPL mutant, MPLT487A, observed in a non-Down syndrome childhood AMKL that induces a myeloproliferative disease in mouse bone marrow transplantation assay.
Malinge
Sébastien
S
Institut National de la Santé et de la Recherche Scientifique (INSERM), E0210, Paris, France.
Ragu
Christine
C
Della-Valle
Veronique
V
Pisani
Didier
D
Constantinescu
Stefan N
SN
Perez
Christelle
C
Villeval
Jean-Luc
JL
Reinhardt
Dirk
D
Landman-Parker
Judith
J
Michaux
Lucienne
L
Dastugue
Nicole
N
Baruchel
André
A
Vainchenker
William
W
Bourquin
Jean-Pierre
JP
Penard-Lacronique
Virginie
V
Bernard
Olivier A
OA