Human Flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival

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

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

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 xenogcneic 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.

Original languageEnglish
Pages (from-to)7358-7367
Number of pages10
JournalJournal of Immunology
Volume180
Issue number11
DOIs
Publication statusPublished - Jan 1 2008

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Granulocyte-Macrophage Progenitor Cells
Hematopoietic Stem Cells
Cell Survival
Hematopoiesis
Acute Myeloid Leukemia
Stem Cells
Myeloid Progenitor Cells
Receptor Protein-Tyrosine Kinases
Fetal Blood
Granulocytes
Homeostasis
Cell Death
Bone Marrow
Macrophages
Maintenance
Mutation
Survival
Population

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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Human Flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival. / Kikushige, Yoshikane; Yoshimoto, Goichi; Miyamoto, Toshihiro; Iino, Tadafumi; Mori, Yasuo; Iwasaki, Hiromi; Niiro, Hiroaki; Takenaka, Katsuto; Nagafuji, Koji; Harada, Mine; Ishikawa, Fumihiko; Akashi, Koichi.

In: Journal of Immunology, Vol. 180, No. 11, 01.01.2008, p. 7358-7367.

Research output: Contribution to journalArticle

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