ESTABLISHMENT OF HUMAN ACUTE MYELOGENOUS LEUKEMIA LINES SECRETING INTERLEUKIN-1-BETA IN SCID MICE

A reproducible in vivo model of human acute myelogeneous leukemia (AML ) was established in severe combined immunodeficient (SCID) mice. The AML-CL and AML-PS lines were originated from leukemic blasts purified respectively from the peripheral blood of a 27-year-old woman with pre viously untreated hyperleukocytotic AML and from the bone marrow of a 61-year-old man during the third leukemic relapse. The 2 lines were ma intained and serially transplanted i.p. in SCID mice. AML-PS and AML-C L produced ascitogenous gross tumors after approximately 4 and 6 weeks , respectively, and all mice died within 6-8 weeks. Microscopic evalua tion of different organs at autopsy showed massive involvement of bone marrow, liver and spleen, though with differences in the tumor burden s for the 2 lines (AML-CL > AML-PS). Flow cytometric analysis document ed the spread of leukemic cells to bone marrow, peuipheral blood and s pleen. AML-PS and AML-CL cells show an immunophenotypic profile (CD13( +), CD33(+)) and cytogenetic findings similar to freshly isolated blas ts. Interleukin-1 beta (IL-1 beta) gene expression was observed by Nor thern blot analysis in leukemic cells from AML-CL and AML-PS SCID mice . After 24 hr of culture both lines released IL-1 beta in culture supe rnatants. High levels of circulating IL-1 beta were secreted in plasma of tumor-bearing mice. This AML-SCID murine model could contribute to an understanding of the mechanisms of AML growth in vivo and the poss ible role of the autocrine production of IL-1 beta in promoting cell g rowth. (C) 1995 Wiley-Liss, Inc.