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Published on: January 20, 2019
Induction of endoplasmic reticulum calcium pump expression during early leukemic B cell differentiation
Lamia Aït Ghezali1,2, Atousa Arbabian3, Hervé Roudot1,2,4
1Institut National de la Santé et de la Recherche Médicale, U978, Bobigny, France.
Insights
Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA) are crucial for B cell function. This study reveals SERCA3 expression increases during B cell differentiation, suggesting its role in regulating this process and potential as a new marker.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Endoplasmic reticulum (ER) calcium dynamics are vital for B lymphocyte functions, including maturation, survival, and activation.
- Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA) are key enzymes responsible for calcium accumulation within the ER.
- Understanding SERCA expression changes during B cell differentiation and leukemia is crucial due to its impact on lymphocyte function.
Purpose of the Study:
- To investigate SERCA expression modulation during the differentiation of leukemic precursor B lymphoblast cell lines.
- To compare SERCA levels with established B lymphoid differentiation markers and mature B cells.
- To assess the impact of SERCA inhibition on the differentiation process.
Main Methods:
- Pharmacologically induced differentiation of E2A-PBX1 fusion oncoprotein-carrying leukemic precursor B lymphoblast cell lines.
- Quantitative analysis of SERCA protein expression levels.
- Comparison of SERCA expression in leukemic cells versus mature B cells.
- Pharmacological inhibition of SERCA-dependent calcium transport.
Main Results:
- Leukemic cells express SERCA2 and SERCA3, with significantly lower SERCA3 levels compared to mature B cells.
- Phorbol ester-induced differentiation led to increased SERCA3 expression.
- Inhibition of SERCA activity during differentiation impaired the process.
Conclusions:
- ER calcium pump composition changes, with increased SERCA3 expression, during precursor B acute lymphoblastic leukemia cell differentiation.
- A functional link exists between SERCA activity and the regulation of B cell differentiation.
- SERCA3 may serve as a novel marker for studying early B cell phenotypes.
Background:
Endoplasmic reticulum (ER) calcium storage and release play important roles in B lymphocyte maturation, survival, antigen-dependent cell activation and immunoglobulin synthesis. Calcium is accumulated in the endoplasmic reticulum (ER) by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes). Because lymphocyte function is critically dependent on SERCA activity, it is important to understand qualitative and quantitative changes of SERCA protein expression that occur during B lymphoid differentiation and leukemogenesis.
Methods:
In this work we investigated the modulation of SERCA expression during the pharmacologically induced differentiation of leukemic precursor B lymphoblast cell lines that carry the E2A-PBX1 fusion oncoprotein. Changes of SERCA levels during differentiation were determined and compared to those of established early B lymphoid differentiation markers. SERCA expression of the cells was compared to that of mature B cell lines as well, and the effect of the direct inhibition of SERCA-dependent calcium transport on the differentiation process was investigated.
Results:
We show that E2A-PBX1+ leukemia cells simultaneously express SERCA2 and SERCA3-type calcium pumps; however, their SERCA3 expression is markedly inferior to that of mature B cells. Activation of protein kinase C enzymes by phorbol ester leads to phenotypic differentiation of the cells, and this is accompanied by the induction of SERCA3 expression. Direct pharmacological inhibition of SERCA-dependent calcium transport during phorbol ester treatment interferes with the differentiation process.
Conclusion:
These data show that the calcium pump composition of the ER is concurrent with increased SERCA3 expression during the differentiation of precursor B acute lymphoblastic leukemia cells, that a cross-talk exists between SERCA function and the control of differentiation, and that SERCA3 may constitute an interesting new marker for the study of early B cell phenotype.
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