ACUTE LEUKEMIAS ASSOCIATED WITH THE 4-11 CHROMOSOME-TRANSLOCATION HAVE REARRANGED IMMUNOGLOBULIN HEAVY-CHAIN GENES

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 66  (1) , 33-38
Abstract
Studies of acute leukemia with the 4;11 translocation have yielded conflicting results regarding the lineage of the cell of origin in this disease. The state of Ig genes in tumor cells from 2 affected patients, immunophenotyped their leukemic cells using a number of monoclonal antibody reagents with specificities for lymphoid or myelomonocytic antigens, and the malignant cells were examined by EM. DNA was extracted from leukemic bone marrow cells and hybridized with radiolabeled DNA fragment probes specific for the constant region of Ig H chain and .kappa. and .lambda. L chain genes. Autoradiographs revealed rearrangement of both allelic H chain genes, but a germline configuration of L 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 [ALL] or T antigens. They did not have sheep erythrocyte receptors nor did they express surface or cytoplasmic Ig or B cell precursor determinants. EM 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 ALL and pre-B-ALL cells, but not for T-ALL or acute myelogenous leukemia cells. Peroxidase was undetectable in cells from both patients. 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.

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