Hypothesis: The Leukemias—Proliferative or Accumulative?

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Abstract
Contrary to the traditional concept, in many instances the leukemias are characterized by an essentially normal or slower individual leukocyte generation time, impaired maturation, altered cell release into the circulation, and prolonged survival of the "leukemic" cell, resulting in a progressive accretion of the potentially divisible cell population arrested in intermediary phases of development. We have come to a critical reorientation in our thinking of the leukemias and neoplasia in general. Continued expansion along conventional lines might be profitably complemented by another program aimed at correction of the leukemic process by encouraging maturation without cellular destruction. The significance of this moment is the inevitable realization that the dream of a cell specific "magic bullet" which would jam the metabolic machinery of the "leukemic cell" may instead correct that defective mechanism by aiding the leukocyte to mature properly. Efforts to accelerate or correct the altered maturation may offer additional approaches to the treatment of the leukemias with or without conventional chemotherapy. A reevaluation of the leukemias and possibly other neoplasms as disorders primarily of accumulation rather than proliferation may be a useful working hypothesis to encourage newer therapeutic approaches.