부산대학교 도서관

Childhood acute myeloid leukemia (AML) is a hematological malignancy in which tumor burden is continuously replenished by leukemic-initiating cells (ICs), which proliferate slowly and are refractory to chemotherapeutic agents. We investigated whether interleukin (IL)-12, an immuno-modulatory cytokine with anti-tumor activity, may target AML blasts (CD45+CD33+) and populations known to contain leukemia ICs (that is, CD34+CD38−, CD33+CD38+ and CD44+CD38− cells). We demonstrate for the first time that: i) AML blasts and their CD34+CD38−, CD33+CD38+, CD44+CD38− subsets express the heterodimeric IL-12 receptor (IL-12R), ii) AML cells injected subcutaneously into NOD/SCID/Il2rg−/− (NSG) mice developed a localized tumor mass containing leukemic ICs and blasts that were virtually eliminated by IL-12 treatment, iii) AML cells injected intravenously into NSG mice engrafted within the first month in the spleen, but not in bone marrow or peripheral blood. At this time, IL-12 dramatically dampened AML CD45+CD33+, CD34+CD38−, CD33+CD38+ and CD44+CD38− populations, only sparing residual CD33+CD38+ cells that did not express IL-12Rβ2. From 30 to 60 days after the initial inoculum, these IL-12-unresponsive cells expanded and metastasized in both control and IL-12-treated NSG mice. Our data indicate that the absence of IL-12Rβ2 in pediatric AML cells favours leukemia progression in NOD/SCID/IL2Rγc-deficient mice. [ABSTRACT FROM AUTHOR]