Leukemia: Recent Advances in Biology and Treatment

Leukemia currently accounts for some 10 percent of cancers, and maintains an even greater position in terms of its human impact because it so frequently strikes children and young people. Though the leukemias have been incurable until quite recently, enormous advances have been made in the understanding of their basic biology and in medical intervention. In addition, they occupy an essential role as a model for research on oncologic pathogenesis and therapeutic investigations of human cancers. Volume 28 of the continuing UCLA Symposia on Molecular and Cellular Biology is devoted to reviewing these recent advances in leukemia biology and treatment and to projecting future research directions in this active field. Editors Robert Gale and David Golde have arranged the 53 papers from a symposium in January 1985 into seven sections: oncogenes and chromosomes, viruses, growth factors and receptors, hematopoietic stem cells, pathogenesis, pharmacology, and therapy of leukemia. As in other areas of oncology, research in leukemia has yielded much progress in the laboratory, with relatively few recent advances in actual patient treatment. Understandably, then, the first three chapters concerning the genetic, viral, and hormonal aspects of leukemias somewhat overshadow the clinical reports, with the exception of work on CML, which has proven profitable at both the basic and clinical ends of the spectrum. Certainly the most intellectually satisfying section of this symposium is the very first, which provides an excellent summary of some of the first work definitely to implicate chromosomal translocations and oncogene products in the pathogenesis of leukemias and lymphomas. This sampling of the significant amount of evidence which has accrued over the past five years to implicate the "Philadelphia chromosome" in the induction of CML includes Robert Gale's work, showing that the specific fused transcript in this rearrangement results in the production of a modified oncogenecoded protein bearing tyrosine kinase activity. Other papers in this chapter review the mechanisms of genomic rearrangement in tumor cell lines such as Burkitt's lymphoma and Wilms' tumor. Robert Gallo begins the chapter on viral oncology with a timely historical review of his research on retroviruses, in particular the HTLV-I virus, and the recent renewed interest in these viruses in the pathogenesis of disease. Also included in this section is a fascinating, if rather scantily supported, hypothesis proposing that EBV-infected B lymphocytes may serve as a biological reservoir for HTLV-III retrovirus during the asymptomatic, chronic carrier state in AIDS patients. The next chapter concerns the physiological control mechanisms that hematopoietic growth factors employ in regulating cell number and function and focuses on the ability of certain leukemic cell lines to secrete autostimulatory growth factors. Several papers discuss the idea that certain leukemias may be caused by an abnormal production of stimulatory growth factors by the proliferating malignant cells themselves, thus becoming independent of exogenously produced regulatory factors. Perhaps what is most exciting about these initial chapters concerning basic research in