SVIBOR - Project code: 3-01-251

MINISTRY OF SCIENCE AND TECHNOLOGY

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Project code: 3-01-251


LABORATORY ESTIMATE OF THE MALIGNANCY OF HUMAN ACUTE LEUKEMIA


Main researcher: MARUŠIĆ, MATKO (29254)


Assistants
Type of research: applied
Duration from: 01/01/91. to 12/31/93.
Papers on project (total): 39
Papers on project quoted in Current Contents: 17
Institution name: KBC, Znanstvena jedinica za patobiokemijska i klinička istraživanja, Zagreb (167)
Department/Institute: Department of immunology
Address: Kišpatićeva 12
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0)1 212-079
Summary: Laboratory estamate of malignancy of human leukemic cells is based on a systematic application of a series of laboratory tests and mutual correlations of the results. The tests include determination of immunuphenotypic cytomorphologic and cytochemic characteristics of leukemic cells from the patient's bone marrow, as well as the cells grown in the short and long term in vitro cultures. The results of these analyses are compared with results of incorporation of 3H-thymidine. In paralell granularity and size of the leukemic cells in comparison to normal cells are determined by flow cytometry. The project plans to analyze some 200 bone marrow specimens from leukemic patients within three years. The results of the testing and literature data will constitute basis for designing an informatic system for disgnosis adapted for a PC. The aim of the project is a substantial improvement of laboratory-based estimate of malignancy of acute leukemias, with direct impact on the choice of therapy protocols.

Keywords: acute leukemia, immunophenotyping, cytomorphology, cytochemistry, cell culture, medical informatic system

Research goals: General aim of the project is a substantial improvement od the estimate of malignancy of human leukemic cells, i.e. a higher level of fine differential diagnosis which will have a significant impact on the choice of therapeutic protocols. This will be achieved by a planned, comprehensive application of a number of laboratory tests which asses the biological characteristics of leukemic cells. 1. A comprehensive flow-cytometric analysis of leukemic cells includes immunophenotyping of leukemic cells and cell cycle analysis, with double staining and analysis of expression of cell differentiation markers in different phases of the cell cycle. The analysis should also allow better positioning of leukemic blasts on two-parameter flow cytometric displays and thus allow reliable analysis of cell samples with relatively low fraction of blasts. 2. Assessment of proliferative potential of leukemic cells will be achieved with short-term cultivation and 3-H-thymidine incorporation in leukemic blasts. This data is complementary to those that will be obtained by approach described as the aim no. 1. 3. In vitro cultivation of leukemic bone marrow cells will provide data on clonogenic potential of both normal and leukemic cells from the tested samples. Addition of various growth factors (e.g., LIF) to the cultures will allow an additional level of differentiation of malignant potential of leukemic cells as well as that of the preserved potential of normal bone marrow stem cells. This approach is applicable to both two-week and long-term bone marrow cultures. 4. Routine citologic and citochemical analysis of leukemic bone marrow samples will be correlated with more sophisticated test listed above; together, they will offer more information than is provided by their simple summing up. Shortly, a comprehensive application of routine and modern laboratoty methods on all leukemic bone marrow samples and their mutual correlation should provide a significantly better insight into the biology of leukemic cells and thus yield both new scientific information and improvement of the diagnosis.

COOPERATION - INSTITUTIONS


  1. Name of institution: MD Anderson Cancer Center, Dpt. of Experimental Radiotherapy
    Type of institution: Other
    Type of cooperation: Joint publishing of scientific papers
    City: 77030 - Houston, USA
Other information about the project.
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