TSLP as a Potential Therapy in the Treatment of CRLF2 B Cell Acute Lymphoblastic Leukemia

Alkashgari, Hossam; Ruiz-Jimenez, Caleb; Stoian, Cornelia; Coats, Jacqueline S.; Báez, Ineavely; Chirshev, Evgeny; Martinez, Shannalee R.; Dovat, Sinisa; Francis-Boyle, Olivia L; Casiano, Carlos A.; Payne, Kimberly J.

doi:10.3390/ijms24010474

Cited by 4 publications

(2 citation statements)

References 36 publications

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“…CRLF2 overexpression has been widely confirmed to be associated with adverse outcomes in B cell acute lymphoblastic leukemia (B-ALL) [ 45 ]. It has been shown that high-dose of thymic stromal lymphopoietin (TSLP) can induce apoptosis, impeding the proliferation and migration of CRLF2 B-ALL tumor cells [ 46 ]. Furthermore, the synergistic combination of the JAK1/2 kinase inhibitor ruxolitinib with conventional treatment has demonstrated enhanced efficacy in CRLF2-altered B-ALL [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

Full-spectral genome analysis of natural killer/T cell lymphoma highlights impacts of genome instability in driving its progression

Chen,

Huang,

Hong

et al. 2024

Genome Med

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Background Natural killer/T cell lymphoma (NKTCL) is a clinically and genetically heterogeneous disease with poor prognosis. Genome sequencing and mutation characterization provides a powerful approach for patient stratification, treatment target discovery, and etiology identification. However, previous studies mostly concentrated on base-level mutations in primary NKTCL, whereas the large-scale genomic alterations in NKTCL and the mutational landscapes in relapsed/refractory NKTCL remain largely unexplored. Methods Here, we assembled whole-genome sequencing and whole-exome sequencing data from 163 patients with primary or relapsed/refractory NKTCL and compared their somatic mutational landscapes at both nucleotide and structure levels. Results Our study not only confirmed previously reported common NKTCL mutational targets like STAT3, TP53, and DDX3X but also unveiled several novel high-frequency mutational targets such as PRDM9, DST, and RBMX. In terms of the overall mutational landscape, we observed striking differences between primary and relapsed/refractory NKTCL patient groups, with the latter exhibits higher levels of tumor mutation burden, copy number variants (CNVs), and structural variants (SVs), indicating a strong signal of genomic instability. Complex structural rearrangements such as chromothripsis and focal amplification are also significantly enriched in relapsed/refractory NKTCL patients, exerting a substantial impact on prognosis. Accordingly, we devised a novel molecular subtyping system (i.e., C0–C4) with distinct prognosis by integrating potential driver mutations at both nucleotide and structural levels, which further provides an informative guidance for novel treatments that target these specific driver mutations and genome instability as a whole. Conclusions The striking differences underlying the mutational landscapes between the primary and relapsed/refractory NKTCL patients highlight the importance of genomic instability in driving the progression of NKTCL. Our newly proposed molecular subtyping system is valuable in assisting patient stratification and novel treatment design towards a better prognosis in the age of precision medicine.

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Section: Resultsmentioning

confidence: 99%

Full-spectral genome analysis of natural killer/T cell lymphoma highlights impacts of genome instability in driving its progression

Chen,

Huang,

Hong

et al. 2024

Genome Med

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“…Furthermore, it is important to underline that the sfTSLP is not only necessary for homeostasis, but it is also involved in carcinogenesis [ 1 , 29 , 36 ]. In human lung cancer, sfTSLP mRNA is significantly more expressed in the intratumoural tissue compared to the peritumoural area [ 37 ].…”

Section: Tslp Isoformsmentioning

confidence: 99%

Thymic Stromal Lymphopoietin (TSLP), Its Isoforms and the Interplay with the Epithelium in Allergy and Asthma

Smolińska

Antolín‐Amérigo

Popescu

et al. 2023

IJMS

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Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine that has emerged as a critical player in the development and progression of allergy and asthma. It is primarily produced by epithelial cells and functions as a potent immune system activator. TSLP acts through interaction with its receptor complex, composed of the TSLP receptor (TSLPR) and interleukin-7 receptor alpha chain (IL-7Rα), activating downstream complex signalling pathways. The TSLP major isoform, known as long-form TSLP (lfTSLP), is upregulated in the airway epithelium of patients with allergic diseases. More research is warranted to explore the precise mechanisms by which short-form TSLP (sfTSLP) regulates immune responses. Understanding the dynamic interplay between TSLP and the dysfunctional epithelium provides insights into the mechanisms underlying allergy and asthma pathogenesis. Targeting TSLP represents an important therapeutic strategy, as it may upstream disrupt the inflammatory cascade and alleviate symptoms associated with allergic inflammation.

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Integration analysis using bioinformatics and experimental validation on the clinical and biological significance of TSLP in cancers

Qu,

Liu,

Jiang

et al. 2023

Cellular Signalling

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TSLP as a Potential Therapy in the Treatment of CRLF2 B Cell Acute Lymphoblastic Leukemia

Cited by 4 publications

References 36 publications

Full-spectral genome analysis of natural killer/T cell lymphoma highlights impacts of genome instability in driving its progression

Full-spectral genome analysis of natural killer/T cell lymphoma highlights impacts of genome instability in driving its progression

Thymic Stromal Lymphopoietin (TSLP), Its Isoforms and the Interplay with the Epithelium in Allergy and Asthma

Integration analysis using bioinformatics and experimental validation on the clinical and biological significance of TSLP in cancers

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