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SGK1 repression by WT1 may confer a survival advantage to leukemic cells under stress conditions
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Journal Article
SGK1 repression by WT1 may confer a survival advantage to leukemic cells under stress conditions
2025
Overview
Increased
WT1
mRNA levels are pervasive in acute myeloid leukemia (AML), and this marker has been used to assess the leukemic compartment size after chemotherapy or hematopoietic cell transplants. Little is known about the effects of
WT1
on the leukemic cells and their targets. This work used data obtained from gene expression arrays performed on AML samples with high and low
WT1
mRNA levels to pinpoint genes that WT1 can regulate. We singled out
SGK1
, which showed an inverse correlation between its mRNA levels and
WT1
in leukemic cell lines and AML samples. In cellular models, forced expression of
WT1
reduced mRNA and protein levels of
SGK1
. Furthermore,
WT1
repressed the SGK1 promoter activity, and accordingly, WT1 knockdown showed an increased expression of
SGK1
. We also detected an inverse correlation between
WT1
and
SGK1
during leukemic cell-line differentiation.
WT1
genetic knockdown displayed decreased cell viability under nutrient deprivation. By contrast,
SGK1
knockdown or pharmacologic inhibition increased resistance to apoptosis in response to serum starvation, acting on cell cycle progression. The effects of
SGK1
targeting in hematologic conditions merit further investigation.
Publisher
Springer Berlin Heidelberg,Springer Nature B.V
Subject
/ Arrays
/ Gene Expression Regulation, Leukemic
/ Genomes
/ Genomics
/ Humans
/ Immediate-Early Proteins - antagonists & inhibitors
/ Immediate-Early Proteins - biosynthesis
/ Immediate-Early Proteins - genetics
/ Immediate-Early Proteins - metabolism
/ Leukemia
/ Leukemia, Myeloid, Acute - genetics
/ Leukemia, Myeloid, Acute - metabolism
/ Leukemia, Myeloid, Acute - pathology
/ Medicine
/ Mutation
/ Oncology
/ Plasmids
/ Protein Serine-Threonine Kinases - antagonists & inhibitors
/ Protein Serine-Threonine Kinases - biosynthesis
/ Protein Serine-Threonine Kinases - genetics
