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Role of MAPK Pathway in Cell Differentiation and Cell Proliferation in Early Hematopoietic Progenitors
Author(s) -
Chung Eva,
Hsu Chialin,
Kondo Motonari
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.844.5
Subject(s) - mapk/erk pathway , haematopoiesis , microbiology and biotechnology , cancer research , myeloid , progenitor cell , biology , kinase , protein kinase a , stem cell
During hematopoietic development, hematopoietic stem cells (HSCs) commit to either the myeloid or lymphoid lineage. Recently, we have shown that the mitogen activated protein kinase (MAPK) pathway is involved in granulocyte/macrophage (GM) lineage commitment under physiological conditions. MAPK kinase (MEK) inhibitors resulted in reduced numbers of granulocyte/macrophage (GM) colonies from HSCs. In addition, the MAPK pathway has been implicated in many types of cancers, including leukemias and lymphomas. Specifically, MEK and its downstream target, extracellular signal‐regulated kinase (Erk), have been shown to be constitutively active in some types of human leukemias. While many studies have been done using cell lines transfected with constitutively active MEK or Erk, no such studies have been conducted with primary cells. In this study, we introduced the constitutively active form of MEK into HSCs and injected the cells into lethally irradiated mice. Our data demonstrates that HSCs transduced with constitutively active MEK leads to massive expansion of granulocytes and macrophages, which is characteristic of chronic myelomonocytic leukemia (CMML) in humans. We are currently characterizing the disease and defining the role of the MEK/ERK pathways in malignant transformation in HSCs.