Monitoring of engraftment and progression of acute lymphoblastic leukemia in individual NOD/SCID mice

Objective. The aim of this study was to develop an animal model for human acute lymphoblastic leukemia (ALL) in which the kinetics and characteristics of leukemia can be sequentially monitored in individual mice. Materials and Methods. NOD/SCID mice were inoculated intravenously with primary ALL. Progression of leukemia was monitored throughout the development of disease by determination of absolute leukemic cell counts (LCC) in peripheral blood. Results. LCC as low as 10(4) leukemic cells/mL blood could be detected. ALL cells from 5 of 5 patients engrafted, and after identification of the first leukemic cells in peripheral blood, LCC increased exponentially. Leukemic cells showed specificity of homing to spleen and bone marrow, and LCC strongly correlated with the level of leukemic engraftment in these organs throughout disease progression, demonstrating that LCC are representative for overall leukemic burden. Cytogenetic analysis of leukemic cells recovered after six successive in vivo transfers revealed no major karyotypic changes as compared to primary cells, and selection of the dominant clones was observed. This selection process was reflected by an increase in the rate of leukemic progression as compared to the first inoculation, demonstrating the accuracy with which kinetics of leukemic progression can be studied by determination of LCC, Conclusions. This model is suitable for detailed studies of kinetics and characteristics of ALL in vivo, and it may be useful for monitoring effects of novel therapeutic regimens. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc

Expression of co-stimulatory and adhesion molecules and chemokine or apoptosis receptors on acute myeloid leukaemia:high CD40 and CD11a expression correlates with poor prognosis

The expression of adhesion and co-stimulatory molecules. and chemokine and death receptors such as tumour necrosis factor (TNF) and FAS on acute myeloid leukaemia (AML) may influence the biology of the disease and response to chemotherapy and immunotherapy. In this study, we analysed the expression of these molecules in 99 AML patients using monoclonal antibodies and flow cytometry, and correlated the expression with French-American-British (FAB) classification and survival. The following molecules were studied: the co-stimulatory molecules CD80. CD86 and CD40: the adhesion molecules CD11a-c, CD31. CD43. CD50, CD54, CD102. CD58 and CD62L: the chemokine receptor CXCR4: and the death receptors TNFR1 and TNFR2 and FAS. The expression of all molecules was significantly higher in the M4/M5 FAB subgroups except for CD80, CD43. CD54 and CD62L. The AML M3 subgroup had a significant lower expression of CD11a (P=0.02) and CD11c (P=0.03). Five-year survival was significantly shorter in cases of high CD40 expression [>20% positive cells. relative risk (RR) 2.56, P=0.02] or high CD11a expression (>80% positive cells, RR 2.6. P=0.03). This effect was most prominently present in the AML M4/M5 FAB subgroups. We conclude that the expression levels of adhesion and co-stimulatory molecules, CXCR4 and apoptosis-receptors are predominantly FAB subtype-related with high CD40 and CD11a expression as poor prognostic factors