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The FLT3 Internal Tandem Duplication (FLT3ITD) mutation is common in adult acute myeloid leukemia (AML) but rare in early childhood AML. It is not clear why this difference occurs. Here we show that Flt3ITD and cooperating Flt3ITD/Runx1 mutations cause hematopoietic stem cell depletion and myeloid progenitor expansion during adult but not fetal stages of murine development. In adult progenitors, FLT3ITD simultaneously induces self-renewal and myeloid commitment programs via STAT5-dependent and STAT5-independent mechanisms, respectively. While FLT3ITD can activate STAT5 signal transduction prior to birth, this signaling does not alter gene expression until hematopoietic progenitors transition from fetal to adult transcriptional states. Cooperative interactions between Flt3ITD and Runx1 mutations are also blunted in fetal/neonatal progenitors. Fetal/neonatal progenitors may therefore be protected from leukemic transformation because they are not competent to express FLT3ITD target genes. Changes in the transcriptional states of developing hematopoietic progenitors may generally shape the mutation spectra of human leukemias.
Pubmed ID: 27879203
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An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE, documented on February 1st, 2022. Software application for genetic analysis of classical biometric traits like blood pressure or height that are caused by a combination of polygenic inheritance and complex environmental forces. (entry from Genetic Analysis Software)
View all literature mentionsSoftware to graphically browse results of clustering and other analyses from Cluster.
View all literature mentionsSoftware package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.
View all literature mentionsMus musculus with name B6.129-Flt3tm1Dgg/J from IMSR.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsMus musculus with name B6.Cg-Commd10Tg(Vav1-icre)A2Kio/J from IMSR.
View all literature mentionsMus musculus with name B6.129S6-Stat5a/Stat5btm2Mam/Mmjax from MMRRC.
View all literature mentionsMus musculus with name B6.129P2-Runx1tm1Tani/J from IMSR.
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Mus musculus with name STOCK Ptprcb Thy1
Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsMus musculus with name B6.129P2-Runx1tm1Tani/J from IMSR.
View all literature mentionsMus musculus with name B6.129S6-Stat5a/Stat5btm2Mam/Mmjax from MMRRC.
View all literature mentionsMus musculus with name B6.Cg-Tg(Mx1-cre)1Cgn/J from IMSR.
View all literature mentionsSoftware R package. Methods for Cluster analysis. Performs variety of types of cluster analysis and other types of processing on large microarray datasets.
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Mus musculus with name STOCK Ptprcb Thy1
Software package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.
View all literature mentionsMus musculus with name B6.Cg-Commd10Tg(Vav1-icre)A2Kio/J from IMSR.
View all literature mentionsMus musculus with name B6.129-Flt3tm1Dgg/J from IMSR.
View all literature mentionsA comprehensive suite of advanced statistics and interactive data visualization specifically designed to reliably extract biological signals from noisy data.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsSoftware R package. Methods for Cluster analysis. Performs variety of types of cluster analysis and other types of processing on large microarray datasets.
View all literature mentionsMus musculus with name B6.Cg-Tg(Mx1-cre)1Cgn/J from IMSR.
View all literature mentionsA comprehensive suite of advanced statistics and interactive data visualization specifically designed to reliably extract biological signals from noisy data.
View all literature mentions