Growth and differentiation factors as cancer therapeutics

Abbreviations used ADCC, antibody-dependent cyto- toxicity; ANLL, acute non-lymphoblastic leukemias; APL, acute promyelocytic leukemia; AML, acute myel- oid leukemia; ATRA, all-trans-retinoic acid; CML, chronic myelogenous leukemia; CSF, colony-stimulating factor; DBD, DNA-binding domain; DMSO, dimethyl- sulfoxide; HMBA, hexamethylenebisacetamide; IL-1, -2, etc., interleukin-1, -2, etc.; LBD, ligand-binding domain; MDS, myelodysplastic syndromes; PKC, protein kinase C; RAR, retinoic recepotr; RXR, retinoid X receptor; TNF, tumor necrosis factor further division and are destined to undergo programmed cell death. Another line of evidence suggesting that growth and maturation factors may be operative in some form of cancers is the observation that patients with neuroblas- toma and germ cell tumors can show maturational effects in the tumor biopsies post treatment. It is not known whether this relates to the treatment since occasional spontaneous maturation had been seen prior to effective therapy for these cancers. These lines of evidence have led some researchers and clinicians to speculate that cancer- ous growth remains under some degree of control by dif- ferentiation and growth factors and that these processes might be augmented or altered therapeutically. A number of observations suggest that differentiation of human myeloid leukemic cells occurs in vivo. The most obvious example is chronic myeloid leukemia (CML), where glucose-6-phosphate dehydrogenase (G6PD) poly- morphism revealed the derivation of mature granulocytes, red cells, and platelets from the leukemic clone. Similar analysis revealed differentiation of acute myeloid leukemia (AML) clones to red blood cells and platelets in some patients (95), and the presence of Auer rods in mature neu- trophils of AML patients in remission and persistence of cytogenetic abnormalities in the absence of normal meta- phases in patients with AML in clinical remission (26, 89).