Details

Autor(en) / Beteiligte

• Kikushige, Yoshikane
• Yoshimoto, Goichi
• Miyamoto, Toshihiro
• Iino, Tadafumi
• Mori, Yasuo
• Iwasaki, Hiromi
• Niiro, Hiroaki
• Takenaka, Katsuto
• Nagafuji, Koji
• Harada, Mine
• Ishikawa, Fumihiko
• Akashi, Koichi

Titel

Human Flt3 Is Expressed at the Hematopoietic Stem Cell and the Granulocyte/Macrophage Progenitor Stages to Maintain Cell Survival

Ist Teil von

• The Journal of immunology (1950), 2008-06, Vol.180 (11), p.7358-7367

Ort / Verlag

United States: Am Assoc Immnol

Erscheinungsjahr

2008

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• FLT3/FLK2, a member of the receptor tyrosine kinase family, plays a critical role in maintenance of hematopoietic homeostasis, and the constitutively active form of the FLT3 mutation is one of the most common genetic abnormalities in acute myelogenous leukemia. In murine hematopoiesis, Flt3 is not expressed in self-renewing hematopoietic stem cells, but its expression is restricted to the multipotent and the lymphoid progenitor stages at which cells are incapable of self-renewal. We extensively analyzed the expression of Flt3 in human (h) hematopoiesis. Strikingly, in both the bone marrow and the cord blood, the human hematopoietic stem cell population capable of long-term reconstitution in xenogeneic hosts uniformly expressed Flt3. Furthermore, human Flt3 is expressed not only in early lymphoid progenitors, but also in progenitors continuously along the granulocyte/macrophage pathway, including the common myeloid progenitor and the granulocyte/macrophage progenitor. We further found that human Flt3 signaling prevents stem and progenitors from spontaneous apoptotic cell death at least through up-regulating Mcl-1, an indispensable survival factor for hematopoiesis. Thus, the distribution of Flt3 expression is considerably different in human and mouse hematopoiesis, and human FLT3 signaling might play an important role in cell survival, especially at stem and progenitor cells that are critical cellular targets for acute myelogenous leukemia transformation.