Cellular lineages in normal and leukemic hemopoiesis.

Certain human hemopoietic disorders (the clonal hemopathies) originate in pluripotent stem cells. These include acute myeloblastic leukemia (AML), chronic myelocytic leukemia (CML), polycythemia vera (P vera), and idiopathic myelofibrosis. In each affected individual a single abnormal clone becomes dominant, occupying all hematologic spaces. An understanding of the cellular basis of normal hemopoiesis and these diseases requires consideration of stem cell properties, clonal expansion, and the differentiation programs of various myelopoietic lineages. The blast cells of AML provide a test of hypotheses about normal and leukemic hemopoiesis. The suggestion is advanced that these blasts do not develop because normal programs are blocked or aborted, but rather follow novel programs, assembled abnormally from normal components. The finding of individual blast cells expressing markers of more than one lineage simultaneously is advanced as support for this model.