Cytokine hematopoietic function

Cytokine receptors are a group of structurally related receptors, which couple to the JAK-STAT pathway. Cytokine receptors function as homodimers or heterooligomers. They are divided into two main subclasses, class I, which contains receptors for a variety of hematopoietic growth factors and interleukins and class II, which contains receptors for interferons and interleukins 10, 20/24 and 22. 

Stem cell therapy involves infusion of specialized cells utilized to perform specific functions. The traditional use of cell therapy includes harvest and cryopreservation of autologous hematopoietic cells either from the bone marrow (old approach) or mobilization and pheresis of hematopoietic stem cells from peripheral blood using stem cell-mobilizing cytokines such as hematopoietic colony-stimulating factors (G-CSF, GM-CSF) or chemokine inhibitors (AMD-3100). A more recent stem cell source is umbilical cord blood that has rich pleuripotent potential and can engraft at lower doses than bone marrow or mobilized peripheral blood stem cells. 

Dr. Alain Fisher and his research team have successfully treated two infants with XSCIDS, a severe form of SCIDS that occurs only in boys. These patients lack functional T cells and natural killer cells (NK) due to mutations in the % chain of the cytokine receptor family that recognizes interleukins (i.e., IL-2, -4, -7, -9, and -15). Ex vivo gene transfer was employed. The researchers delivered the wild-type sequence for the yc chain cytokine receptor subunit to hematopoietic stem cells isolated from these patients using a nonreplicating murine retrovirus [14,15]. 

Hematopoietic cytokines comprise one of the largest groups of extracellular regulatory molecules and are key mediators of a diverse spectrum of physiological functions that include induction of immune responses, cell proliferation, and differentiation (Gosman, 1993 Cosman et al, 1990 Kishimoto et al, 1994 Nicola and Hilton, 1998 Taga and Kishimoto,... 

In hematopoietic cehs, cytokines also regulate death receptor-mediated pathways. Hematopoietic cytokines, such as IL-3 and erythropoietin in normal cells and BCR-ABL oncoprotein in transformed cells, inhibit transcription of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The inhibition of TRAIL function is sufficient to partially rescue cytokine-deprived cells from apoptosis. Cytokine and BCR-ABL suppression of TRAIL transcription is mediated through phosphorylation and inhibition of the forkhead F0X03a transcription factor. BCR-ABL-induced inhibition of TRAIL transcription in hematopoietic cells may provide a novel mechanism for tumorigenicity in chronic myeloid leukemia. ... 

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