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Using CRISPR/Cas9 Gene Editing to Investigate the Oncogenic Activity of Mutant Calreticulin in Cytokine Dependent Hematopoietic Cells

Using CRISPR/Cas9 Gene Editing to Investigate the Oncogenic Activity of Mutant Calreticulin in Cytokine Dependent Hematopoietic Cells

Published on: January 5, 2018

Alterations of Signaling Pathways in Essential Thrombocythemia with Calreticulin Mutation

Wuhan Hui¹, Wei Zhang¹, Congyan Liu¹

¹Department of Hematology, Xuan Wu Hospital, Capital Medical University, Beijing, People's Republic of China.

Cancer Management and Research

|August 16, 2021

Abstract

Purpose:

Though mutations of the calreticulin (CALR) gene have been identified in essential thrombocythemia patients, the detailed mechanisms for CALR mutations have not been completely clarified. Our study is aimed at characterizing alteration of protein expression in ET patients with mutated CALR and further recognizing possible involvement of signaling pathways associated with CALR mutations.

Patients And Methods:

Protein pathway array was performed to analyze the expression levels of proteins involved in various signaling pathways in peripheral blood neutrophils from 18 ET patients with mutated CALR , 20 ET patients with JAK2 mutation and 20 controls.

Results:

We found 20 proteins differentially expressed in ET patients with mutated CALR compared with healthy controls. These proteins were associated with molecular mechanisms of cancer in ingenuity pathways analysis (IPA) network. We identified top ten canonical pathways which including apoptotic pathways and cellular cytokine pathways might participate in pathogenesis of ET with mutated CALR . Additionally, there were 8 proteins found to be dysregulated differently between ET patients with mutated CALR and those with JAK2 mutation. These proteins might be related to the unique signaling pathways activated by CALR mutation which were different to JAK/STATs pathway by JAK2 mutation.

Conclusion:

Our study demonstrated that numerous alterations of signaling proteins and pathways in ET patients with mutated CALR . These findings could help to gain insights into the pathological mechanisms of ET.

Insights

Mutations in the calreticulin (CALR) gene are linked to essential thrombocythemia (ET). This study reveals significant protein and pathway alterations in ET patients with CALR mutations, offering insights into disease mechanisms.

Area of Science:

Hematology
Molecular Biology
Oncology

Background:

Calreticulin (CALR) gene mutations are observed in essential thrombocythemia (ET).
The precise molecular mechanisms underlying CALR mutations in ET remain incompletely understood.
Characterizing protein expression alterations is crucial for elucidating ET pathogenesis.

Purpose of the Study:

To investigate protein expression changes in ET patients with CALR mutations.
To identify signaling pathways potentially involved in CALR-mutated ET.
To compare molecular profiles between CALR-mutated ET and JAK2-mutated ET.

Main Methods:

Protein pathway array analysis was conducted on neutrophils.
Study included 18 ET patients with CALR mutations, 20 ET patients with JAK2 mutations, and 20 healthy controls.
Ingenuity Pathway Analysis (IPA) was used for network and pathway analysis.

Main Results:

Twenty proteins were differentially expressed in CALR-mutated ET compared to controls, linked to cancer pathways.
Apoptotic and cellular cytokine pathways were identified as potentially participating in CALR-mutated ET pathogenesis.
Eight proteins showed differential dysregulation between CALR-mutated ET and JAK2-mutated ET, suggesting distinct signaling.

Conclusions:

Significant alterations in signaling proteins and pathways are evident in ET patients with CALR mutations.
These findings contribute to a deeper understanding of the pathological mechanisms in ET.
The study highlights potential differences in signaling pathways activated by CALR versus JAK2 mutations.

Read full analysis

Keywords:

CALRdel52 mutation essential thrombocytosis protein pathway array signaling proteins

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