Our ability to detect relapse of acute leukemia is limited at present to traditional morphologic techniques, which lack sensitivity and objectivity.
Specific aim 1 (a) of this proposal is to use a novel multiparameter flow cytometry assay to detect early relapse in acute lymphoblastic leukemia (ALL) by measuring rare strongly common ALL antigen (CALLA) positive cells in the peripheral blood. The success of this assay would permit trial of intensive treatment of patients in """"""""preclinical"""""""" relapse, which is likely to be more successful than current treatment for clinical relapse. The CALLA antigen is also expressed, but much more weakly, on a distinct population of normal bone marrow lymphocytes. These cells are of special interest because they are probably the earliest human B cell progenitor that can be identified by a phenotypic marker. As an easily identifiable progenitor cell, their numbers may reflect the proliferative activity of other hematopoietic progenitor cells in the marrow, and hence their vulnerability to chemotherapy. The clinical correlation of weakly CALLA positive marrow lymphocytes with marrow toxicity of chemotherapy is specific aim 1(b). This unique lymphocyte population has not been extensively characterized because of its rarity in adult bone marrow. Multiparameter flow cytometry and sorting of pediatric bone marrow will permit an investigation of the phenotypic and functional maturation of weakly CALLA positive bone marrow precursors of pre-B cells, which is specific aim 2 of this proposal. Phenotypic studies will be performed to identify the lineage specificity of these cells and find differences between these cells and the strong CALLA positive leukemic cells so that the latter can be detected in marrow by the method used in specific aim 1(a) for blood. Maturation and clonal growth in culture will be induced to permit studies of regulatory factors for differentiation and growth of early B cell precursors. (3)
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