Abstract
We have recently reported inactivation of the tyrosine phosphatase PTPN2 (also known as TC-PTP) through deletion of the entire gene locus in ∼ 6% of T-cell acute lymphoblastic leukemia (T-ALL) cases. T-ALL is an aggressive disease of the thymocytes characterized by the stepwise accumulation of chromosomal abnormalities and gene mutations. In the present study, we confirmed the strong association of the PTPN2 deletion with TLX1 and NUP214-ABL1 expression. In addition, we found cooperation between PTPN2 deletion and activating JAK1 gene mutations. Activating mutations in JAK1 kinase occur in ∼ 10% of human T-ALL cases, and aberrant kinase activity has been shown to confer proliferation and survival advantages. Our results reveal that some JAK1 mutation - positive TALLs harbor deletions of the tyrosine phosphatase PTPN2, a known negative regulator of the JAK/STAT pathway. We provide evidence that down-regulation of Ptpn2 sensitizes lymphoid cells to JAK1-mediated transformation and reduces their sensitivity to JAK inhibition.
| Original language | English |
|---|---|
| Pages (from-to) | 7090-7098 |
| Number of pages | 9 |
| Journal | Blood |
| Volume | 117 |
| Issue number | 26 |
| DOIs | |
| Publication status | Published - Jun 30 2011 |
Fingerprint
ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
PTPN2 negatively regulates oncogenic JAK1 in T-cell acute lymphoblastic leukemia. / Kleppe, Maria; Soulier, Jean; Asnafi, Vahid; Mentens, Nicole; Hornakova, Tekla; Knoops, Laurent; Constantinescu, Stefan; Sigaux, François; Meijerink, Jules P.; Vandenberghe, Peter; Tartaglia, Marco; Foa, Robin; Macintyre, Elizabeth; Haferlach, Torsten; Cools, Jan.
In: Blood, Vol. 117, No. 26, 30.06.2011, p. 7090-7098.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - PTPN2 negatively regulates oncogenic JAK1 in T-cell acute lymphoblastic leukemia
AU - Kleppe, Maria
AU - Soulier, Jean
AU - Asnafi, Vahid
AU - Mentens, Nicole
AU - Hornakova, Tekla
AU - Knoops, Laurent
AU - Constantinescu, Stefan
AU - Sigaux, François
AU - Meijerink, Jules P.
AU - Vandenberghe, Peter
AU - Tartaglia, Marco
AU - Foa, Robin
AU - Macintyre, Elizabeth
AU - Haferlach, Torsten
AU - Cools, Jan
PY - 2011/6/30
Y1 - 2011/6/30
N2 - We have recently reported inactivation of the tyrosine phosphatase PTPN2 (also known as TC-PTP) through deletion of the entire gene locus in ∼ 6% of T-cell acute lymphoblastic leukemia (T-ALL) cases. T-ALL is an aggressive disease of the thymocytes characterized by the stepwise accumulation of chromosomal abnormalities and gene mutations. In the present study, we confirmed the strong association of the PTPN2 deletion with TLX1 and NUP214-ABL1 expression. In addition, we found cooperation between PTPN2 deletion and activating JAK1 gene mutations. Activating mutations in JAK1 kinase occur in ∼ 10% of human T-ALL cases, and aberrant kinase activity has been shown to confer proliferation and survival advantages. Our results reveal that some JAK1 mutation - positive TALLs harbor deletions of the tyrosine phosphatase PTPN2, a known negative regulator of the JAK/STAT pathway. We provide evidence that down-regulation of Ptpn2 sensitizes lymphoid cells to JAK1-mediated transformation and reduces their sensitivity to JAK inhibition.
AB - We have recently reported inactivation of the tyrosine phosphatase PTPN2 (also known as TC-PTP) through deletion of the entire gene locus in ∼ 6% of T-cell acute lymphoblastic leukemia (T-ALL) cases. T-ALL is an aggressive disease of the thymocytes characterized by the stepwise accumulation of chromosomal abnormalities and gene mutations. In the present study, we confirmed the strong association of the PTPN2 deletion with TLX1 and NUP214-ABL1 expression. In addition, we found cooperation between PTPN2 deletion and activating JAK1 gene mutations. Activating mutations in JAK1 kinase occur in ∼ 10% of human T-ALL cases, and aberrant kinase activity has been shown to confer proliferation and survival advantages. Our results reveal that some JAK1 mutation - positive TALLs harbor deletions of the tyrosine phosphatase PTPN2, a known negative regulator of the JAK/STAT pathway. We provide evidence that down-regulation of Ptpn2 sensitizes lymphoid cells to JAK1-mediated transformation and reduces their sensitivity to JAK inhibition.
UR - http://www.scopus.com/inward/record.url?scp=79959826613&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959826613&partnerID=8YFLogxK
U2 - 10.1182/blood-2010-10-314286
DO - 10.1182/blood-2010-10-314286
M3 - Article
C2 - 21551237
AN - SCOPUS:79959826613
VL - 117
SP - 7090
EP - 7098
JO - Blood
JF - Blood
SN - 0006-4971
IS - 26
ER -