Dysregulated signaling pathways in the development of CNTRL-FGFR1–induced myeloid and lymphoid malignancies associated with FGFR1 in human and mouse models

Mingqiang Ren, Haiyan Qin, Eiko Kitamura, John K. Cowell

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Myeloid and lymphoid neoplasm associated with FGFR1 is an aggressive disease, and resistant to all the current chemotherapies. To define the molecular etiology of this disease, we have developed murine models of this disease, in syngeneic hosts as well as in nonobese diabetic/severe combined immunodeficiency/interleukin 2Rγnull mice engrafted with transformed human CD341 hematopoietic stem/progenitor cells. Both murine models mimic the human disease with splenohepatomegaly, hypercellular bone marrow, and myeloproliferative neoplasms that progresses to acute myeloid leukemia. Molecular genetic analyses of these model mice, as well as primary human disease, demonstrated that CNTRL-FGFR1, through abnormal activation of several signaling pathways related to development and differentiation of both myeloid and T-lymphoid cells, contribute to overt leukemogenesis. Clonal evolution analysis indicates that myeloid related neoplasms arise from common myeloid precursor cells that retain potential for T-lymphoid differentiation. These data indicate that simultaneously targeting these pathways is essential to successfully treating this almost invariably lethal disease.

Original languageEnglish (US)
Pages (from-to)1007-1016
Number of pages10
JournalBlood
Volume122
Issue number6
DOIs
StatePublished - Aug 8 2013

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Neoplasms
Hematopoietic Stem Cells
Bone Marrow Neoplasms
Clonal Evolution
Severe Combined Immunodeficiency
Chemotherapy
Interleukins
Genetic Models
Myeloid Cells
Stem cells
Acute Myeloid Leukemia
Molecular Biology
Bone
Chemical activation
Lymphocytes
Drug Therapy

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Dysregulated signaling pathways in the development of CNTRL-FGFR1–induced myeloid and lymphoid malignancies associated with FGFR1 in human and mouse models. / Ren, Mingqiang; Qin, Haiyan; Kitamura, Eiko; Cowell, John K.

In: Blood, Vol. 122, No. 6, 08.08.2013, p. 1007-1016.

Research output: Contribution to journalArticle

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