Stem cell origin of human myeloid blood cell neoplasms.

Studies with G6PD and molecular probes indicate that the myeloid leukemias and the chronic myeloproliferative disorders are clonal diseases. The G6PD data indicate that chronic myelogenous leukemia, polycythemia vera and essential thrombocythemia involve stem cells pluripotent for granulocytes, erythrocytes, megakaryocytes and lymphocytes. Agnogenic myeloid metaplasia is also a clonal disease that involves multipotent hematopoietic stem cells. However, myelofibrosis, the predominant clinical manifestation, occurs secondarily and is not a component of the abnormal clonal proliferation. Acute nonlymphocytic leukemia is a clonal disease, but G6PD studies suggest that there are at least two forms of this leukemia. In one type of ANL, the involved stem cells exhibit pluripotent differentiative expression. In another type of ANL, differentiative expression is largely restricted to the granulocytic pathway. The heterogeneity of ANL has both clinical and pathogenetic implications.