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)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R23)
Project #
1R23CA039569-01
Application #
3446700
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1985-05-01
Project End
1988-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
Schools of Medicine
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Ryan, D H (1993) Adherence of normal and neoplastic human B cell precursors to the bone marrow microenvironment. Blood Cells 19:225-41;discussion 241-4
Ryan, D H; Nuccie, B L; Abboud, C N (1992) Inhibition of human bone marrow lymphoid progenitor colonies by antibodies to VLA integrins. J Immunol 149:3759-64
Liesveld, J L; Abboud, C N; Duerst, R E et al. (1989) Characterization of human marrow stromal cells: role in progenitor cell binding and granulopoiesis. Blood 73:1794-800
Liesveld, J L; Abboud, C N; Looney, R J et al. (1988) Expression of IgG Fc receptors in myeloid leukemic cell lines. Effect of colony-stimulating factors and cytokines. J Immunol 140:1527-33
Ryan, D H; Fallon, M A; Horan, P K (1988) Flow cytometry in the clinical laboratory. Clin Chim Acta 171:125-73
Anderson, C L; Ryan, D H; Looney, R J et al. (1987) Structural polymorphism of the human monocyte 40 kilodalton Fc receptor for IgG. J Immunol 138:2254-6
Rosenfeld, S I; Ryan, D H; Looney, R J et al. (1987) Human Fc gamma receptors: stable inter-donor variation in quantitative expression on platelets correlates with functional responses. J Immunol 138:2869-73
Ryan, D H; Chapple, C W; Kossover, S A et al. (1987) Phenotypic similarities and differences between CALLA-positive acute lymphoblastic leukemia cells and normal marrow CALLA-positive B cell precursors. Blood 70:814-21
Abboud, C N; Duerst, R E; Frantz, C N et al. (1986) Lysis of human fibroblast colony-forming cells and endothelial cells by monoclonal antibody (6-19) and complement. Blood 68:1196-200
Ryan, D; Kossover, S; Mitchell, S et al. (1986) Subpopulations of common acute lymphoblastic leukemia antigen-positive lymphoid cells in normal bone marrow identified by hematopoietic differentiation antigens. Blood 68:417-25

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