# Thymic stromal lymphopoietin in leukemia: A double-edged sword?

## TL;DR

Thymic stromal lymphopoietin (TSLP) can both promote and kill leukemia cells depending on the dose and genetic context, offering new treatment possibilities.

## Contribution

First demonstration of TSLP's dual roles in leukemia through proliferation and apoptosis mechanisms.

## Key findings

- TSLP promotes leukemia cell proliferation via CRLF2 signaling.
- High doses of TSLP induce apoptosis in leukemia cells.
- Dose-dependent TSLP effects redefine therapeutic windows for leukemia treatment.

## Abstract

•First demonstration of TSLP's dual roles in leukemia: TSLP promotes proliferation via CRLF2 signaling while inducing apoptosis in specific contexts, revealing its paradoxical tumor-modulating effects.•Elucidates biphasic TSLP regulation: Dose-dependent signaling thresholds determine the proliferation-apoptosis switch, redefining therapeutic windows.•Proposes precision medicine approach: Genetic biomarker-guided TSLP targeting addresses response heterogeneity, enabling personalized treatment strategies.

First demonstration of TSLP's dual roles in leukemia: TSLP promotes proliferation via CRLF2 signaling while inducing apoptosis in specific contexts, revealing its paradoxical tumor-modulating effects.

Elucidates biphasic TSLP regulation: Dose-dependent signaling thresholds determine the proliferation-apoptosis switch, redefining therapeutic windows.

Proposes precision medicine approach: Genetic biomarker-guided TSLP targeting addresses response heterogeneity, enabling personalized treatment strategies.

Thymic stromal lymphopoietin (TSLP) is a cytokine expressed by various cell types. It is involved in the development of allergies, autoimmune diseases, and cancers. TSLP affects immune responses and disease pathogenesis by binding to a heterodimeric receptor complex. In leukemia, particularly acute lymphoblastic leukemia (ALL), the importance of TSLP is being increasingly recognized. It has been shown that TSLP promotes leukemia proliferation by regulating different signaling pathways. However, it has also shown that other gene mutations can occur during this proliferative process, making it impossible to completely cure leukemia by targeting TSLP alone. Additionally, effect of TSLP on leukemia was found to be dose dependent. Whilst low doses were found to support the proliferation of leukemia cells, high doses were found to induce apoptosis in leukemia cells. This review focuses on the dual mechanisms of TSLP in leukemia, providing new insights for leukemia treatment.

Dual Mechanisms of TSLP in Leukemia. This figure was created using Figdraw. Image, graphical abstract