Extracellular NM23 Protein as a Therapeutic Target for Hematologic Malignancies

Figure 3

Extracellular function of NM23-H1 protein derived from tumor (AML) cells on primary cultured normal PBMNC and AML cells. Extracellular NM23-H1 protein promotes the growth/survival of primary AML cells mediated by MAPK activation, STAT activation, and cytokine release [33]. On the other hand, extracellular NM23-H1 protein affects normal PBMNC survival, activates monocytes, and induces cytokine production [34]. Some of these cytokines, especially GM-CSF and IL-1β, directly promote the survival/growth of primary cultured AML cells. Moreover, NM23-H1 induces immunosuppressive cytokine, such as IL-10. Therefore, the cytokine-inducing effect of extracellular NM23-H1 protein on normal PBMNC may be associated with a poor prognosis in AML. Taken together, these observations suggest that extracellular NM23-H1 may play an important role in the malignant progression of leukemia and that inhibitors of extracellular NM23-H1 protein or inhibitors of extracellular functions of this protein should be evaluated for their treatment.