Survivin expression in the bone marrow of patients with severe congenital neutropenia

Carlsson, Göran; Boxhammer, Sandra; Garwicz, Daniel; Henter, Jan‐Inge; Palmblad, Jan; Nordenskjöld, Magnus; Porwit, Anna; Fadeel, Bengt

doi:10.1038/leu.2008.258

Cited by 3 publications

(1 citation statement)

References 8 publications

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“…Furthermore, mitochondrial release of cytochrome c was also increased in myeloid progenitors from patients with HAX1 mutations but not in controls 35,47 . Interestingly, these patients had elevated survivin levels in myeloid cells 58 . Morphologic studies and laboratory evidence suggest that apoptosis and removal of the weakened cells by marrow macrophages is the final step in this pathway.…”

Section: Mechanisms/pathophysiologymentioning

confidence: 92%

Severe congenital neutropenias

Skokowa

Dale

Touw

et al. 2017

Nat Rev Dis Primers

285

318

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Severe congenital neutropenias are a heterogeneous group of rare haematological diseases that are characterized by impaired maturation of neutrophil granulocytes. Patients with severe congenital neutropenia are prone to recurrent, often life-threatening infections beginning in their first months of life. The most frequent pathogenetic defects are autosomal dominant mutations in ELANE, which encodes neutrophil elastase, and autosomal recessive mutations in HAX1, whose product contributes to the activation of the granulocyte-colony stimulating factor (G-CSF) signalling pathway. The pathophysiological mechanisms of these conditions are the object of extensive research and are not fully understood. Furthermore, severe congenital neutropenias may predispose to myelodysplastic syndromes or acute myeloid leukaemia. Molecular events in the malignant progression include acquired mutations in CSF3R (encoding G-CSF receptor) and subsequently in other leukaemia-associated genes (such as RUNX1) in a majority of patients. Diagnosis is based on clinical manifestations, blood neutrophil count, bone marrow examination, and genetic and immunological analyses. Daily subcutaneous G-CSF administration is the treatment of choice and leads to a substantial increase in blood neutrophils count, reduction of infections and drastic improvement of quality of life. Haematopoietic stem cell transplantation is the alternative treatment. Regular clinical assessments (including yearly bone marrow examinations) to monitor treatment course and detect chromosomal abnormalities (e.g. trisomy 21, monosomy 7) as well as somatic pre-leukaemic mutations are recommended.

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Section: Mechanisms/pathophysiologymentioning

confidence: 92%

Severe congenital neutropenias

Skokowa

Dale

Touw

et al. 2017

Nat Rev Dis Primers

285

318

View full text Add to dashboard Cite

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Hax-1: a regulator of calcium signaling and apoptosis progression with multiple roles in human disease

Simmen¹

2011

Expert Opinion on Therapeutic Targets

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Generation of a Novel Transgenic Mouse Model for Bioluminescent Monitoring of Survivin Gene Activity in Vivo at Various Pathophysiological Processes

Cheng

Ling

et al. 2010

The American Journal of Pathology

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Survival has been implicated to play an important role in various pathophysiological processes. However, because of a lack of appropriate animal models, the role and dynamic expression of survivin during pathophysiology are not well defined. We generated a human survivin gene promoter-driven luciferase transgenic mouse model (SPlucTg) so that dynamic survivin gene activity can be monitored during various pathophysiological conditions using in vivo imaging. Our results show that, consistent with survivin positivity in testis , luciferase activity in normal SPlucTg mice was detected in the testis of male mice. Furthermore, similar to the known requirement of transient expression of survivin for pathophysiological responses, we observed a transient luciferase expression in castrated SPlucTg male mice after supplement of androgen. Significantly, it was reported that survivin expression turns on during mouse liver injury and regeneration; a transient and dose-dependent luciferase expression in the mouse liver was observed after administration of carbon tetrachloride into SPlucTg mice. We further demonstrated that luciferase activity closely correlates with endogenous survivin expression. We also demonstrated that only a subset of cells expresses survivin, and its expression overlaps with the expression of several stem cell markers tested. Thus, we have generated a unique animal model for analysis of diverse pathophysiological processes and possible stem cell distribution/ activity in vivo.

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Survivin expression in the bone marrow of patients with severe congenital neutropenia

Cited by 3 publications

References 8 publications

Severe congenital neutropenias

Severe congenital neutropenias

Hax-1: a regulator of calcium signaling and apoptosis progression with multiple roles in human disease

Generation of a Novel Transgenic Mouse Model for Bioluminescent Monitoring of Survivin Gene Activity in Vivo at Various Pathophysiological Processes

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