TY - JOUR
T1 - Absence of IL-12RΒ2 in CD33 + CD38 + pediatric acute myeloid leukemia cells favours progression in NOD/SCID/IL2RγC- deficient mice
AU - Ferretti, E.
AU - Montagna, D.
AU - Di Carlo, E.
AU - Cocco, C.
AU - Ribatti, D.
AU - Ognio, E.
AU - Sorrentino, C.
AU - Lisini, D.
AU - Bertaina, A.
AU - Locatelli, F.
AU - Pistoia, V.
AU - Airoldi, I.
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
KW - AML
KW - cytokine receptor
KW - cytokines
UR - http://www.scopus.com/inward/record.url?scp=84856751793&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856751793&partnerID=8YFLogxK
U2 - 10.1038/leu.2011.213
DO - 10.1038/leu.2011.213
M3 - Article
C2 - 21844875
AN - SCOPUS:84856751793
VL - 26
SP - 225
EP - 235
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 2
ER -