Absence of IL-12RΒ2 in CD33 + CD38 + pediatric acute myeloid leukemia cells favours progression in NOD/SCID/IL2RγC- deficient mice

E. Ferretti, D. Montagna, E. Di Carlo, C. Cocco, D. Ribatti, E. Ognio, C. Sorrentino, D. Lisini, A. Bertaina, F. Locatelli, V. Pistoia, I. Airoldi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)225-235
Number of pages11
JournalLeukemia
Volume26
Issue number2
DOIs
Publication statusPublished - Feb 2012

Keywords

  • AML
  • cytokine receptor
  • cytokines

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Fingerprint Dive into the research topics of 'Absence of IL-12RΒ2 in CD33 + CD38 + pediatric acute myeloid leukemia cells favours progression in NOD/SCID/IL2RγC- deficient mice'. Together they form a unique fingerprint.

Cite this