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Table 2 Inhibition of transcription factor functions by FLT3-ITD

From: Downstream molecular pathways of FLT3 in the pathogenesis of acute myeloid leukemia: biology and therapeutic implications

Author Target Responsible signaling pathway Mechanisms of the action
Mizuki et al. [43] C/EBPα, PU.1 unknown Down-regulates myeloid transcription factor C/EBPα and PU.1 expression.
Scheijen et al. [54] FOXO3a Akt Inhibition of FOXO3a leads to the upregulation of p27KIP1 and Bim gene expression. These promote cell survival and proliferation.
Zheng et al. [55] C/EBPα, PU.1 unknown Down-regulates myeloid transcription factor C/EBPα and PU.1 expression. Those may play a role in myeloid differentiation block.
Radomska et al. [56] C/EBPα MEK/ERK Phosphorylates serine 21 of C/EBPα, results in the differentiation block of MV4;11 cells.
Takahashi et al. [47] PLZF MEK/ERK Dissociates its transcriptional co-repressor SMRT, inhibits the growth suppressor function of PLZF, leading to abnormal cell growth.
Takahashi et al. [60] Runx1/AML1 unknown Runx1/AML1-SMRT interaction is disrupted by FLT3-ITD, leading to the aberrant expression of the Runx1/AML1target gene p21WAF1/CIP1.