At one extreme are tumors that grow rapidly and exponentially and show no evidence of maturation, such as Burkitt's lymphoma. At the other extreme is CML, a malignancy in which, in the early stages, expansion of the tumor stem cell pool is limited and the range of maturation is complete. Experimental studies have shown that various factors influence tumor cell differentiation. Experimental myeloid leukemia cells may respond to both maturation and growth factors by differentiating into cells that behave normally. The virus-induced cancer erythroleukemia undergoes some degree of differentiation under various experimental conditions, as evidenced by an increase in hemoglobin production.
Many antitumor agents cause differentiation in experimental myeloid leukemias.
The molecular mechanisms underlying tumor cell differentiation are under study. Differentiation in the HL60 line is associated with a marked decrease in transcription of the c- myc oncogene. Clinical trials of retinoids for the treatment of preneoplastic and early neoplastic lesions such as bronchial metaplasia in heavy smokers, recurrent superficial bladder cancers, xeroderma pigmentosum, and recurrent keratoacanthomas are under way. In preleukemia, or refractory anemia with blasts, leukemia cells showing some degree of aberrant, and presumably arrested, maturation are generally identifiable in the marrow in low and stable numbers. The development of specific chromosomal probes has permitted detection of clonality in differentiated cells.