Distinct signaling programs associated with progression of FGFR1 driven leukemia in a mouse model of stem cell leukemia lymphoma syndrome

Maria J Silva, Chang Sheng Chang, Tianxiang Hu, Haiyan Qin, Eiko Kitamura, Lesleyann Hawthorn, Mingqiang Ren, John Kenneth Cowell

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Constitutive activation of FGFR1 as a result of chromosome translocations is responsible for the development of a hematopoietic stem cell disorder that progresses to AML. We have developed a syngeneic mouse model of BCR-FGFR1 driven AML and used RNASeq to define gene expression signatures associated with disease progression. The development of the leukemic stem cells (LSC) is associated with a profound downregulation of specific transcription factors that normally maintain stem cell quiescence as well as cell adhesion and motility gene sets related to confinement to the stem cell niche. A prominent feature of the LSCs is the upregulation of genes involved in T-cell function, activation, migration and development. Despite this apparent T-cell priming in the LSCs, however, the majority of these genes are subsequently inactivated in the leukemic blast cells that derive from them. These studies provide insights into the molecular etiology of development and progression of FGFR1 driven AML.

Original languageEnglish (US)
Pages (from-to)1566-1573
Number of pages8
JournalGenomics
Volume111
Issue number6
DOIs
StatePublished - Dec 2019

Fingerprint

Lymphoma
Leukemia
Stem Cells
Genes
Stem Cell Niche
T-Lymphocytes
Hematopoietic Stem Cells
Transcriptome
Cell Adhesion
Cell Movement
Disease Progression
Transcription Factors
Up-Regulation
Down-Regulation
Chromosomes

Keywords

  • BCR-FGFR1
  • FGFR1
  • Gene expression
  • RNASeq
  • SCLL
  • Stem cells

ASJC Scopus subject areas

  • Genetics

Cite this

Distinct signaling programs associated with progression of FGFR1 driven leukemia in a mouse model of stem cell leukemia lymphoma syndrome. / Silva, Maria J; Chang, Chang Sheng; Hu, Tianxiang; Qin, Haiyan; Kitamura, Eiko; Hawthorn, Lesleyann; Ren, Mingqiang; Cowell, John Kenneth.

In: Genomics, Vol. 111, No. 6, 12.2019, p. 1566-1573.

Research output: Contribution to journalArticle

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AU - Kitamura, Eiko

AU - Hawthorn, Lesleyann

AU - Ren, Mingqiang

AU - Cowell, John Kenneth

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AB - Constitutive activation of FGFR1 as a result of chromosome translocations is responsible for the development of a hematopoietic stem cell disorder that progresses to AML. We have developed a syngeneic mouse model of BCR-FGFR1 driven AML and used RNASeq to define gene expression signatures associated with disease progression. The development of the leukemic stem cells (LSC) is associated with a profound downregulation of specific transcription factors that normally maintain stem cell quiescence as well as cell adhesion and motility gene sets related to confinement to the stem cell niche. A prominent feature of the LSCs is the upregulation of genes involved in T-cell function, activation, migration and development. Despite this apparent T-cell priming in the LSCs, however, the majority of these genes are subsequently inactivated in the leukemic blast cells that derive from them. These studies provide insights into the molecular etiology of development and progression of FGFR1 driven AML.

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