Why Does α-Interferon Work in Chronic Granulocytic; Leukaemia?

Experimental evidence is presented to demonstrate that α-interferon (αIFN) has its most potent antiproliferative effect upon the late progenitor compartment of myelopoiesis. As this compartment is greatly expanded in chronic granulocytic leukaemia (CGL), it is suggested that the clinical efficacy of αIFN therapy in CGL derives from inhibition of late progenitor division and an attendant reduction in neutrophil production. Furthermore, the reduction in Philadelphia positive: (Ph +) metaphases and increase in Philadelphia negative (Ph -) metaphases seen in some patients on αIFN therapy may be due to there being proportionally more αIFN-sensitive cells within the Ph+ compartment. As the tumour bulk of the Ph+ clone decreases, the suppressive effect that it has over the Ph - compartment ma,y be eroded, allowing upgrowth of Ph- myelopoiesis and reconstitution of a normal karyotype.