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[Inhibitors of hematopoiesis: from physiology to therapy]
1Service de Médecine C Chimiothérapie, Institut Gustave Roussy, Villejuif.
A balance of both stimulatory and inhibitory factors interfere with gross and precise hematopoiesis regulation. A number of inhibitory molecules may endeavour a physiological role (cytokines like TGF beta, TNF alpha, platelet factor 4 PF4, Interferons, MIP1 alpha or peptides like p-EEDCK, Ac-SDKP. Hemopoietic primitive stem cells are relatively spared from chemo- or radiotherapy toxicity when they stay in a quiescent G0 state. They suffer from repeated toxic treatments when they undergo cycling. Molecules like the AcSDKP (seraspenide) inhibit in a reversible way stem cell and progenitors cycling, affording them a significant degree of protection from chemotherapy (cytarabine, cyclophosphamide, 5FU, AZT) and ionizing radiation toxicity. A clinical phase Ib study suggests protective effects from cytarabine toxicity.
A balance of both stimulatory and inhibitory factors interfere with gross and precise hematopoiesis regulation. A number of inhibitory molecules may endeavour a physiological role (cytokines like TGF beta, TNF alpha, platelet factor 4 PF4, Interferons, MIP1 alpha or peptides like p-EEDCK, Ac-SDKP. Hemopoietic primitive stem cells are relatively spared from chemo- or radiotherapy toxicity when they stay in a quiescent G0 state. They suffer from repeated toxic treatments when they undergo cycling. Molecules like the AcSDKP (seraspenide) inhibit in a reversible way stem cell and progenitors cycling, affording them a significant degree of protection from chemotherapy (cytarabine, cyclophosphamide, 5FU, AZT) and ionizing radiation toxicity. A clinical phase Ib study suggests protective effects from cytarabine toxicity.