Abstract
Previous studies have shown that the interleukin-12 receptor β2 (IL-12Rβ2) gene is expressed in normal naive, germinal center and memory B cells but not in their malignant counterparts. The aim of this study was to investigate (i) whether the IL-12Rβ2 gene is silenced in B-cell acute lymphoblastic leukemia (B-ALL) cells, and (ii) what the functional implications of such silencing for tumor growth are. Here, we show that although mature B cells expressed both chains of the IL-12R, normal pro-B and pre-B cells failed to express the IL-12Rβ2 chain. Similarly, primary tumor cells from pediatric pro-B, early pre-B, and pre-B ALL (30 cases) did not express the IL-12Rβ2 chain. IL-12Rβ2 gene silencing in B-ALL was found to depend on methylation of a CpG island in exon 1. Such methylation was not detected in normal early B cells that when differentiated into mature B cells expressed the IL-12Rβ2 gene. Detection of IL-12Rβ2 mRNA and protein in the tumorigenic 697 pre-B-ALL cell line allowed to perform functional experiments in severe combined immunodeficient/ nonobese diabetic mice receiving 697 cells with or without human recombinant IL-12 (hrIL-12). hrIL-12 administration reduced tumor growth and metastasis through antiproliferative and proapoptotic rather than antiangiogenic, activities. In conclusion, epigenetic silencing of the IL-12Rβ2 gene represents a novel mechanism of tumor escape for B-ALL cells.
| Original language | English |
|---|---|
| Pages (from-to) | 3978-3980 |
| Number of pages | 3 |
| Journal | Cancer Research |
| Volume | 66 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Apr 15 2006 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Methylation of the IL-12Rβ2 gene as novel tumor escape mechanism for pediatric B-acute lymphoblastic leukemia cells. / Airoldi, Irma; Cocco, Claudia; Di Carlo, Emma; Disarò, Silvia; Ognio, Emanuela; Basso, Giuseppe; Pistoia, Vito.
In: Cancer Research, Vol. 66, No. 8, 15.04.2006, p. 3978-3980.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Methylation of the IL-12Rβ2 gene as novel tumor escape mechanism for pediatric B-acute lymphoblastic leukemia cells
AU - Airoldi, Irma
AU - Cocco, Claudia
AU - Di Carlo, Emma
AU - Disarò, Silvia
AU - Ognio, Emanuela
AU - Basso, Giuseppe
AU - Pistoia, Vito
PY - 2006/4/15
Y1 - 2006/4/15
N2 - Previous studies have shown that the interleukin-12 receptor β2 (IL-12Rβ2) gene is expressed in normal naive, germinal center and memory B cells but not in their malignant counterparts. The aim of this study was to investigate (i) whether the IL-12Rβ2 gene is silenced in B-cell acute lymphoblastic leukemia (B-ALL) cells, and (ii) what the functional implications of such silencing for tumor growth are. Here, we show that although mature B cells expressed both chains of the IL-12R, normal pro-B and pre-B cells failed to express the IL-12Rβ2 chain. Similarly, primary tumor cells from pediatric pro-B, early pre-B, and pre-B ALL (30 cases) did not express the IL-12Rβ2 chain. IL-12Rβ2 gene silencing in B-ALL was found to depend on methylation of a CpG island in exon 1. Such methylation was not detected in normal early B cells that when differentiated into mature B cells expressed the IL-12Rβ2 gene. Detection of IL-12Rβ2 mRNA and protein in the tumorigenic 697 pre-B-ALL cell line allowed to perform functional experiments in severe combined immunodeficient/ nonobese diabetic mice receiving 697 cells with or without human recombinant IL-12 (hrIL-12). hrIL-12 administration reduced tumor growth and metastasis through antiproliferative and proapoptotic rather than antiangiogenic, activities. In conclusion, epigenetic silencing of the IL-12Rβ2 gene represents a novel mechanism of tumor escape for B-ALL cells.
AB - Previous studies have shown that the interleukin-12 receptor β2 (IL-12Rβ2) gene is expressed in normal naive, germinal center and memory B cells but not in their malignant counterparts. The aim of this study was to investigate (i) whether the IL-12Rβ2 gene is silenced in B-cell acute lymphoblastic leukemia (B-ALL) cells, and (ii) what the functional implications of such silencing for tumor growth are. Here, we show that although mature B cells expressed both chains of the IL-12R, normal pro-B and pre-B cells failed to express the IL-12Rβ2 chain. Similarly, primary tumor cells from pediatric pro-B, early pre-B, and pre-B ALL (30 cases) did not express the IL-12Rβ2 chain. IL-12Rβ2 gene silencing in B-ALL was found to depend on methylation of a CpG island in exon 1. Such methylation was not detected in normal early B cells that when differentiated into mature B cells expressed the IL-12Rβ2 gene. Detection of IL-12Rβ2 mRNA and protein in the tumorigenic 697 pre-B-ALL cell line allowed to perform functional experiments in severe combined immunodeficient/ nonobese diabetic mice receiving 697 cells with or without human recombinant IL-12 (hrIL-12). hrIL-12 administration reduced tumor growth and metastasis through antiproliferative and proapoptotic rather than antiangiogenic, activities. In conclusion, epigenetic silencing of the IL-12Rβ2 gene represents a novel mechanism of tumor escape for B-ALL cells.
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U2 - 10.1158/0008-5472.CAN-05-4418
DO - 10.1158/0008-5472.CAN-05-4418
M3 - Article
VL - 66
SP - 3978
EP - 3980
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 8
ER -