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Studies of acute leukemia with the 4;11 translocation have yielded conflicting results regarding the lineage of the cell of origin in this disease. To investigate this issue further, we have examined the state of immunoglobulin genes in tumor cells from two affected patients, immunopheno-typed their leukemic cells using a number of monoclonal antibody reagents with specificities for lymphoid or myelo-monocytic antigens, and examined the malignant cells by electron microscopy. DNA was extracted from leukemic bone marrow cells and hybridized with radiolabeled DNA fragment probes specific for the constant region of immunoglobulin heavy chain and κ and X light chain genes. Autoradiographs revealed rearrangement of both allelic heavy chain genes, but a germline configuration of light chain genes in both cases. Surface marker analysis showed that blasts from both patients expressed HLA-DR and the myeloid antigens Leu-M1, 1C2, 2D1, and 4B3, but lacked common acute lymphocytic leukemia antigen or T antigens. Furthermore, they did not have sheep erythrocyte receptors nor did they express surface or cytoplasmic immunoglobulin or B cell precursor determinants. Electron microscopy analysis showed that blast cells from patient 1 exhibited numerous monoribosomes, polyribosomes, and isolated strands of rough endoplasmic reticulum in their cytoplasm. These ultrastructural features are characteristic for both common acute lymphocytic leukemia and pre-B-ALL cells, but not for T-ALL or acute myelogenous leukemia cells. Peroxidase was undetectable in cells from both patients. Our study suggests that this disorder represents a unique subtype of leukemia. The cell of origin may be an early B cell progenitor that shares certain surface antigens with myeloid cells or a stem cell with the potential for both lymphoid and myelomonocytic differentiation. © 1985 by Grune & Stratton, Inc.

Although major progress has been made in the treatment of childhood leukemia, the optimal chemotherapy of acute lymphoblastic leukemia (ALL) in adults has been unclear. In addition, the value of central nervous system prophylaxis (CNS-P) in adults has been assumed, but not established in a systematic fashion. The Southeastern Cancer Study Group has completed a prospective study in which the use of vincristine plus low-dose methotrexate and high-dose prednisone in adult acute lymphoblastic leukemia has produced an 80% (79/99) complete remission rate in patients age 15 yr and over. Younger patients had a significantly higher remission rate but no increase in remission duration. This induction regimen was associated with minimal toxicity. Random assignment to CNS-P or to no prophylaxis, after a multidrug consolidation regimen, has demonstrated a significant prolongation of CNS relapse-free interval (p= 0.008) in favor of CNS-P. CNS-P did not improve hematologic remission duration or survival. All complete remitters were maintained on mercaptopurine, methotrexate, and cyclophosphamide with pulses of prednisone and vincristine; the median time from remission to either hematologic or CNS relapse was 19.3 mo after CNS-P, and survival for these patients was 26.1 mo. We conclude that our current induction regimen is highly effective in adult ALL and that CNS prophylaxis is indicated in such patients.