Establishment of human acute myelogenous leukemia lines secreting interleukin-1 beta in SCID mice.
A reproducible in vivo model of human acute myelogenous 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 previously untreated hyperleukocytotic AML and from the bone marrow of a 61-year-old man during the third leukemic relapse. The 2 lines were maintained and serially transplanted i.p. in SCID mice. AML-PS and AML-CL produced ascitogenous gross tumors after approximately 4 and 6 weeks, respectively, and all mice died within 6-8 weeks. Microscopic evaluation of different organs at autopsy showed massive involvement of bone marrow, liver and spleen, though with differences in the tumor burdens for the 2 lines (AML-CL > AML-PS). Flow cytometric analysis documented the spread of leukemic cells to bone marrow, peripheral blood and spleen. AML-PS and AML-CL cells show an immunophenotypic profile (CD13+, CD33+) and cytogenetic findings similar to freshly isolated blasts. Interleukin-1 beta (IL-1 beta) gene expression was observed by Northern 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 supernatants. 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 possible role of the autocrine production of IL-1 beta in promoting cell growth.
Giavazzi
R
R
Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
Di Berardino
C
C
Garofalo
A
A
Motta
T
T
Gobbi
A
A
Scanziani
E
E
Giudici
G
G
Galli
M
M
Mayo
J G
JG
Barbui
T
T
D000328:Adult; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D016513:Mice, SCID / Q000378:metabolism*; D008875:Middle Aged; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D007375:Interleukin-1