Header

UZH-Logo

Maintenance Infos

Activating mutations in human acute megakaryoblastic leukemia


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.

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.

Statistics

Citations

81 citations in Web of Science®
93 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

222 downloads since deposited on 17 May 2010
14 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2008
Deposited On:17 May 2010 16:57
Last Modified:05 Apr 2016 14:06
Publisher:American Society of Hematology
ISSN:0006-4971
Additional Information:This research was originally published in Blood, 15 November 2008, Vol. 112, No. 10, pp. 4220-4226. Copyright by the American Society of Hematology
Publisher DOI:https://doi.org/10.1182/blood-2008-01-136366
PubMed ID:18755984

Download

Preview Icon on Download
Preview
Filetype: PDF
Size: 1MB
View at publisher