ACUTE NONLYMPHOCYTIC LEUKEMIA - EXPRESSION IN CELLS RESTRICTED TO GRANULOCYTIC AND MONOCYTIC DIFFERENTIATION

Two patients with acute nonlymphocytic leukemia who were heterozygous for the X-chromosome-linked enzyme glucose-6-phosphate dehydrogenase were studied to determine the number and type of cells in which the disease arises. Both type A and B isoenzymes were found in normal tissues, but the myeloblasts showed only one enzyme type, indicating that at the time of study, the disease had a clonal origin. The observation in one patient that erythroid cells did not arise from this clone contrasts with conclusions reached in patients previously studied with chromosomal markers. The results suggest that in this patient, the leukemic clone suppressed expression of normal granulopoiesis but did not inhibit erythroid differentiation from normal progenitors. They suggest also that the disease is heterogeneous. In some patients, the disease is expressed in cells with differentiation restricted to the granulocytemacrophage pathway; in others, it involves stem cells that also differentiate into erythrocytes. This heterogeneity may reflect differences in causation and could have prognostic importance. (N Engl J Med 301:1–5, 1979) THE glucose-6-phosphate dehydrogenase locus can be used to study the origin of neoplasms because it is on the X chromosome and undergoes inactivation. Thus, in females, only one of the two genes regulating glucose-6-phosphate dehydrogenase is active in each somatic cell; women heterozygous at this locus for the usual B gene (GdB) and a common variant, such as GdA or GdA-, have two cell populations, one producing B-type glucose-6-phosphate dehydrogenase and the other A-type isoenzyme. All progeny of a neoplastic stem-cell clone will manifest type B or A enzyme, whereas a tumor that arises from many cells. © 1979, Massachusetts Medical Society. All rights reserved.