Lymphoid Blast Crises of Chronic Myelogenous Leukemia Represent Stages in the Development of B-Cell Precursors

The origin and stage of differentiation of the blast-crisis cells in chronic myelogenous leukemia have remained uncertain. Because immunoglobulin heavy-chain and light-chain genes must undergo a DNA rearrangement during B-cell development but rarely do so in human non-B-cell lineages, we examined these genes in 18 episodes of chronic myelogenous leukemia. In eight of nine episodes of lymphoid blast crisis, heavy-chain genes were rearranged, and in three, rearrangements in light-chain genes were also present. In contrast, cells from chronic myeloid, myeloid blast, and erythroid-like phases retained germ-like immunoglobulin genes. The observed phenotypic markers and gene configurations revealed that most lymphoid blast crises represent stages of development of B-cell precursors. In two separate episodes of lymphoid crisis, cells from a single patient possessed identical heavy-chain but different light-chain-gene configurations. Thus, the precursor cells that monoclonally expand to produce a lymphoid crisis are capable of immunoglobulin-gene rearrangements and represent discrete steps in early B-cell maturation. (N Engl J Med 1983; 309:826–31.) CYTOGENETIC and isoenzyme studies have established that chronic myelogenous leukemia is a clonal proliferative disorder arising from a progenitor cell with a rather pluripotential capacity.^{1 2 3 4 5 6} Studies of glucose-6-phosphate dehydrogenase isoenzymes in female heterozygotes with chronic myelogenous leukemia have revealed that involved granulocytes, erythrocytes, platelets, monocytes, and some lymphocytes displayed only a single glucose-6-phosphate dehydrogenase allele.^{3 4 5 6} This finding indicated that in this disease, cells in multiple hematopoietic lineages could be of clonal origin. Because of this multipotential capacity of the clonally derived cell in chronic myelogenous leukemia, the exact cellular origin and indeed the state of differentiation of the cells comprising.