Molecular Genetics of Acute Promyelocytic Leukemia: A Rationale for “Transcription Therapy” for Cancer

Summary

The last few years have been crucial for the elucidation of the molecular mechanisms underlying the pathogenesis of human leukemia [1]. In particular, more than 80% of myeloid leukemias have been attributed to, or associated with, one or more specific molecular lesions. In the vast majority of cases these molecular events are chromosomal translocations that rearrange the regulatory and coding regions of a variety of genes which encode transcription factors. These proteins can interfere with the normal transduction, at the transcription level, of pivotal cellular processes such as growth, differentiation, and survival. The identification of these lesions renders it possible to reclassify myeloid leukemias according to new “molecular” criteria, and to develop new diagnostic and prognostic tools. Furthermore, the understanding of the aberrant transcriptional mechanisms underlying leukemia pathogenesis allows the development of new therapeutic approaches. In particular, the recent elucidation of the molecular mechanisms underlying the pathogenesis of acute promyelocytic leukemia has allowed us to propose and exploit what we regard as a new concept for the treatment of cancer, which we refer to as “transcription therapy.”