FLT3 ITD- and NOX4-dependent H2O2 production

Stable Identifier
R-HSA-9698758
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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NOX4 catalyzes the synthesis of H2O2 downstream of FLT3 ITD mutants in a STAT5-dependent manner, increasing the levels of reactive oxygen species (ROS) (Jayvavelu et al, 2016a; Sallmyer et al, 2008; Reddy et al, 2011). High ROS levels cause oxidative inactivation of the protein tyrosine phosphatase PTPRJ, also known as DEP1, a negative regulator of FLT3 signaling. In consequence, FLT3 ITD-expressing cells have higher signaling activity than the wild type, as well as increased proliferation (Arora et al, 2011; Godfrey et al, 2012; Kresinsky et al, 2015; Jayavelu et al, 2016a; reviewed in Jayavelu et al, 2016b).

Literature References
PubMed ID Title Journal Year
22438257 Cell transformation by FLT3 ITD in acute myeloid leukemia involves oxidative inactivation of the tumor suppressor protein-tyrosine phosphatase DEP-1/ PTPRJ

Godfrey, R, Arora, D, Bauer, R, Stopp, S, Müller, JP, Heinrich, T, Böhmer, SA, Dagnell, M, Schnetzke, U, Scholl, S, Östman, A, Böhmer, FD

Blood 2012
27666490 NOX-driven ROS formation in cell transformation of FLT3-ITD-positive AML

Jayavelu, AK, Moloney, JN, Böhmer, FD, Cotter, TG

Exp. Hematol. 2016
21072051 NADPH oxidases regulate cell growth and migration in myeloid cells transformed by oncogenic tyrosine kinases

Reddy, MM, Fernandes, MS, Salgia, R, Levine, RL, Griffin, JD, Sattler, M

Leukemia 2011
26308771 NOX4-driven ROS formation mediates PTP inactivation and cell transformation in FLT3ITD-positive AML cells

Jayavelu, AK, Müller, JP, Bauer, R, Böhmer, SA, Lässig, J, Cerny-Reiterer, S, Sperr, WR, Valent, P, Maurer, B, Moriggl, R, Schröder, K, Shah, AM, Fischer, M, Scholl, S, Barth, J, Oellerich, T, Berg, T, Serve, H, Frey, S, Fischer, T, Heidel, FH, Böhmer, FD

Leukemia 2016
18192505 Internal tandem duplication of FLT3 (FLT3/ITD) induces increased ROS production, DNA damage, and misrepair: implications for poor prognosis in AML

Sallmyr, A, Fan, J, Datta, K, Kim, KT, Grosu, D, Shapiro, P, Small, D, Rassool, F

Blood 2008
29880609 Loss of DEP-1 (Ptprj) promotes myeloproliferative disease in FLT3-ITD acute myeloid leukemia

Kresinsky, A, Bauer, R, Schnöder, TM, Berg, T, Meyer, D, Ast, V, König, R, Serve, H, Heidel, FH, Böhmer, FD, Müller, JP

Haematologica 2018
Participants
Participates
Catalyst Activity

NAD(P)H oxidase H2O2-forming activity of NOX4 [plasma membrane]

Disease
Name Identifier Synonyms
acute myeloid leukemia DOID:9119 Leukemia, Myelocytic, acute, acute myeloblastic leukemia, acute myelogenous leukemia, AML - acute Myeloid Leukemia
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Cross References
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