Mitochondria Turnover and Lysosomal Function in Hematopoietic Stem Cell Metabolism.

Hematopoietic stem cells (HSCs) reside in a hypoxic microenvironment that enables glycolysis-fueled metabolism and reduces oxidative stress. Nonetheless, metabolic regulation in organelles such as the mitochondria and lysosomes as well as autophagic processes have been implicated as essential for the determination of HSC cell fate. This review encompasses the current understanding of anaerobic metabolism in HSCs as well as the emerging roles of mitochondrial metabolism and lysosomal regulation for hematopoietic homeostasis.

[Efficacy of thrombopoietin in bone marrow failure].

Thrombopoietin (Thpo) is a hematopoietic cytokine that regulates the production of megakaryocyte/platelet lineage cells and maintains hematopoietic stem and progenitor cells (HSPCs). While Thpo directly stimulates the proliferation of HSPCs, it also maintains HSCs in quiescence to form a reserve pool of HSCs in the bone marrow. Moreover, Thpo activates mitochondria and induces HSC differentiation to megakaryocyte/platelet lineage cells. Being void of instigating anti-Thpo antibody formation in vivo, the use of Thpo receptor agonists (Mpl agonists) transcends the use of recombinant Thpo in the treatment of immune thrombocytopenia. Since its invention, the therapeutic indication of Mpl agonists has extended to the treatment of bone marrow failure in aplastic anemia. As the clinical application of Mpl agonists expands, a detailed investigation of the function and effect of Mpl agonists on physiological HSCs and bone marrow failure is necessary.

[Ageing of hematopoietic stem cells].

The frequency of clonal hematopoiesis in humans vastly increases with aging. Older adults may develop one or several clones and this condition is called clonal hematopoiesis of indeterminate potential (CHIP). Recent genetic analyses have identified the genes inducing CHIP. These mutant genes are detected frequently in elderly people and this condition is a precursor of hematopoietic neoplasms. The prevalence of hematopoietic neoplasms in patients with CHIP is tenfold that in those without CHIP. Consequently, the mechanism of aging and leukemogenesis of hematopoietic stem cells is being understood. Furthermore, the efficacy of senolysis, selectively removing scenescent cells from tissues, has been demonstrated in mice. The clinical application of senolysis is anticipated shortly.

Isolated granulocytic sarcoma of the small intestine successfully treated with chemotherapy and bone marrow transplantation.

Isolated primary granulocytic sarcoma is a rare disease that presents as an extramedullary tumor of myeloid lineage cells. Most patients subsequently develop acute myelogenous leukemia (AML) within a short period, and their prognosis is poor. Herein, we report the case of a 33-year-old woman with a primary isolated granulocytic sarcoma which originated in the small intestine. After she recovered from surgery, she received intensive chemotherapy equivalent to that for AML, followed by allogeneic bone marrow transplantation from an HLA-matched, unrelated donor. Four years after the transplantation, she remains in complete remission without graft-versus-host disease or any other symptoms. This case illustrates the effectiveness of our therapeutic strategy for isolated granulocytic sarcoma, not only with surgical resection of the tumor and intensive chemotherapy equivalent to that for AML, but also with allogeneic bone marrow transplantation, performed while no sign of AML is observed.