chapter  4
18 Pages

Functional complementation of cytokine receptor signaling by BCR/ABL Eugene Y Koh, George Q Daley

Homeostasis within the hematopoietic system is tightly controlled by over a dozen hematopoietic growth factors, termed cytokines, that drive progenitor proliferation, facilitate differentiation, and enhance cell survival.1,2

Under normal circumstances blood cell populations maintain a steady balance of production and turnover, but in response to hemorrhage, hypoxia, or infection, enhanced cytokine generation stimulates the bone marrow to boost blood cell production. Bone marrow pathology can be viewed as alterations of cell proliferation, differentiation, and death – processes intimately linked to cytokines. Understanding cytokine regulation is particularly pertinent to the myeloproliferative disorders (MPDs), an interesting class of bone marrow diseases characterized by massive expansion in blood cell numbers but relatively normal differentiation and cellular function. The molecular lesions in

these disorders appear less disruptive to the overall program of hematopoiesis than do the mutations underlying the more aggressive acute leukemias, which have equally robust hyperproliferation but greatly compromised differentiation and marrow function. Understanding how cytokine regulation is altered in the MPDs may shed light on the molecular basis of hematopoietic homeostasis itself.