The Leo Sachs' legacy: a pioneer's journey through hematopoiesis.

Leo Sachs spent almost his entire scientific career in Israel, at the Weizmann Institute of Science, and became a worldwide renowned scientist for his pioneering studies in normal hematopoiesis, its breakdown in leukemia and the suppression of malignancy by inducing differentiation, thereby bypassing genetic defects that give rise to malignancy. The cell culture system he established in the early 1960s for the clonal development of normal hematopoietic cells, made it possible to discover the proteins that regulate the viability, proliferation and differentiation of different blood cell lineages, the molecular basis of normal hematopoiesis and the changes that drive leukemia. His studies established significant general concepts including: a) the value of a multi-gene cytokine network in regulating the viability, number and development of different cell types; b) the existence of alternative pathways that give flexibility to development in both normal and cancer cells; c) the response of some cancer cells to normal regulators of development; d) suppression of myeloid leukemia by inducing differentiation, bypassing malignancy-driving genetic defects; e) identification of chromosomes that control tumor suppression; f) discovering apoptosis as a major mechanism by which WT-p53 suppresses malignancy and g) the ability of hematopoietic cytokines to suppress apoptosis in both normal and leukemic cells. It is gratifying that Leo had the good fortune to witness his pioneering discoveries and ideas move from the basic science stage to effective clinical applications, augmenting normal hematopoiesis in patients with various hematopoietic deficiencies, in patients requiring hematopoietic stem cell transplantation and in the suppression of malignancy by inducing differentiation and apoptosis.