Abstract |
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.
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Authors | Sébastien Malinge, Christine Ragu, Veronique Della-Valle, Didier Pisani, Stefan N Constantinescu, Christelle Perez, Jean-Luc Villeval, Dirk Reinhardt, Judith Landman-Parker, Lucienne Michaux, Nicole Dastugue, André Baruchel, William Vainchenker, Jean-Pierre Bourquin, Virginie Penard-Lacronique, Olivier A Bernard |
Journal | Blood
(Blood)
Vol. 112
Issue 10
Pg. 4220-6
(Nov 15 2008)
ISSN: 1528-0020 [Electronic] United States |
PMID | 18755984
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Adult
- Aged
- Animals
- Cell Line, Tumor
- Child
- Child, Preschool
- Down Syndrome
(genetics, metabolism)
- Female
- Humans
- Infant
- Infant, Newborn
- Leukemia, Megakaryoblastic, Acute
(genetics, metabolism)
- Male
- Mice
- Mice, Inbred BALB C
- Middle Aged
- Mutation
- Neoplasm Proteins
(biosynthesis, genetics)
- Neoplasm Transplantation
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