Nat Commun: Targeting PI3K/AKT overactivation induces cell death in chronic lymphocytic leukemia

In chronic lymphocytic leukemia (CLL), autonomous autoimmune reactive BCR (B cell receptor) signaling contributes to the survival of tumor cells , and currently established targeted therapy strategies mainly focus on inhibiting oncogenic kinases in the BCR pathway , By depriving the relevant signals, leading to cell death
.

In chronic lymphocytic leukemia (CLL), autonomous autoimmune reactive BCR (B cell receptor) signaling helps tumor cells survive.
In chronic lymphocytic leukemia (CLL), autonomous autoimmune reactive BCR (B cell receptor) Body) signal contributes to the survival and immunity of tumor cells

However, despite the initial remission of CLL, patients often develop relapsed and refractory disease or eventually progress to Richter syndrome, and treatment options are limited
.

In this study, the researchers proposed the following hypothesis, that is, by targeting the excessive activation of the PI3K/AKT (phosphatidylinositol 3-phosphate/AKT) signaling pathway to trigger the death of CLL cells
.

The results show that genetically overactivating the PI3K/AKT signal transduction pathway or blocking the activity of the inhibitory phosphatase SHIP1 can induce the acute cell death process of CLL cells

Targeting the excessive activation of PI3K/AKT (phosphatidylinositol 3-phosphate/AKT) signaling pathway triggers the death of CLL cells

Acute AKT1 activation is harmful to CLL cells

Acute AKT1 activation is harmful to CLL cells

Mechanism studies have shown that inhibition of SHIP1 will cause an increase in AKT activity, resulting in an increase in mitochondrial respiration and an excessive accumulation of reactive oxygen species (ROS), leading to the death of CLL cells with immunogenic characteristics
.

CLL cell survival requires SHIP1 activity to inhibit AKT signaling

CLL cell survival requires SHIP1 activity to inhibit AKT signaling

All in all, the results of this study reveal that CLL cells are heavily dependent on the activity of PI3K/AKT to ensure their continued proliferation and survival, and to avoid ROS-induced cell death .
The results of this study also indicate that SHIP1's transient inhibition or CLL's A potential treatment strategy
.

CLL cells rely heavily on the activity of PI3K/AKT to ensure their continued proliferation and survival, and avoid ROS-induced cell death.
CLL cells rely heavily on the activity of PI3K/AKT to ensure their continued proliferation and survival, and avoid ROS-induced cell death

Original source:

Ecker, V.

, Stumpf, M.
, Brandmeier, L.

Targeted PI3K/AKT-hyperactivation induces cell death in chronic lymphocytic leukemia.

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