Reduced proliferation of CD34(+) cells from patients with acute myeloid leukemia after gene transfer of INPP5D.
Standard
Reduced proliferation of CD34(+) cells from patients with acute myeloid leukemia after gene transfer of INPP5D. / Metzner, A; Precht, Clarissa; Fehse, Boris; Fiedler, Walter; Stocking, C; Günther, A; Mayr, Georg W.; Jücker, Manfred.
In: GENE THER, Vol. 16, No. 4, 4, 2009, p. 570-573.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Reduced proliferation of CD34(+) cells from patients with acute myeloid leukemia after gene transfer of INPP5D.
AU - Metzner, A
AU - Precht, Clarissa
AU - Fehse, Boris
AU - Fiedler, Walter
AU - Stocking, C
AU - Günther, A
AU - Mayr, Georg W.
AU - Jücker, Manfred
PY - 2009
Y1 - 2009
N2 - Acute myeloid leukemia (AML) is a malignant disease characterized by deregulated proliferation of immature myeloid cells. Constitutive activation of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is frequently detected in approximately 50-70% of AML patients. The gene INPP5D encodes the SH2-containing inositol 5-phosphatase 1 (SHIP1), which is a negative regulator of PI3K/AKT signaling. After lentiviral-mediated gene transfer of INPP5D into CD34(+) cells derived from AML patients (n=12) the granulocyte macrophage-colony stimulating factor (GM-CSF)-dependent proliferation was reduced in all samples analyzed (average 86%; range 72-93%). An enzymatically inactive form of SHIP1 (D672A) had no effect. In addition, SHIP1 reduced the autonomous proliferation of CD34(+) cells from a patient with a secondary AML who had a very high peripheral blast count (300 x 10(9) l(-1)). These data show that SHIP1 can effectively block GM-CSF-dependent and autonomous proliferation of AML cells.
AB - Acute myeloid leukemia (AML) is a malignant disease characterized by deregulated proliferation of immature myeloid cells. Constitutive activation of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is frequently detected in approximately 50-70% of AML patients. The gene INPP5D encodes the SH2-containing inositol 5-phosphatase 1 (SHIP1), which is a negative regulator of PI3K/AKT signaling. After lentiviral-mediated gene transfer of INPP5D into CD34(+) cells derived from AML patients (n=12) the granulocyte macrophage-colony stimulating factor (GM-CSF)-dependent proliferation was reduced in all samples analyzed (average 86%; range 72-93%). An enzymatically inactive form of SHIP1 (D672A) had no effect. In addition, SHIP1 reduced the autonomous proliferation of CD34(+) cells from a patient with a secondary AML who had a very high peripheral blast count (300 x 10(9) l(-1)). These data show that SHIP1 can effectively block GM-CSF-dependent and autonomous proliferation of AML cells.
M3 - SCORING: Zeitschriftenaufsatz
VL - 16
SP - 570
EP - 573
JO - GENE THER
JF - GENE THER
SN - 0969-7128
IS - 4
M1 - 4
ER -