Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells
Andrea PellagattiMario CazzolaAristoteles GiagounidisJanet PerryLuca MalcovatiMatteo Giovanni Della PortaMartin JäderstenSally KillickAmit VermaChris J. NorburyEva Hellström‐LindbergJames S. WainscoatJacqueline Boultwood
279
Citation
75
Reference
10
Related Paper
Citation Trend
The haematopoietic system is a classical stem cell hierarchy that maintains all the blood cells in the body. Haematopoietic stem cells (HSCs) are rare, highly potent cells that reside at the apex of this hierarchy and are historically some of the most well studied stem cells in humans and laboratory models, with haematopoiesis being the original system to define functional cell types by cell surface markers. Whilst it is possible to isolate HSCs to near purity, we know very little about the functional activity of markers to purify HSCs. This review will focus on the historical efforts to purify HSCs in humans based on cell surface markers, their putative functions and recent advances in finding functional markers on HSCs.
Stem cell marker
Identification
Cite
Citations (23)
Cite
Citations (514)
Haematopoietic stem cells (HSCs) can supply all blood cells throughout the adult life of individuals. Based on this property, HSCs have been used for bone marrow and cord blood transplantation. Among various stem cells, HSCs were recognized earliest and were studied most extensively, providing a model for other stem cells. Knowledge of HSC regulation has rapidly accumulated of late. Contributions of scientists in Japan to progress HSC biology are here briefly overviewed. Focusing on the original work accomplished in Japan in the last two decades, people who have led such activities are introduced and their relationships with one another are sketched.
Cord blood
Cite
Citations (1)
To produce the wide range of blood and immune cell types, haematopoietic stem cells can “choose” directly from the entire spectrum of blood cell fate-options. Affiliation to a single cell lineage can occur at the level of the haematopoietic stem cell and these cells are therefore a mixture of some pluripotent cells and many cells with lineage signatures. Even so, haematopoietic stem cells and their progeny that have chosen a particular fate can still “change their mind” and adopt a different developmental pathway. Many of the leukaemias arise in haematopoietic stem cells with the bulk of the often partially differentiated leukaemia cells belonging to just one cell type. We argue that the reason for this is that an oncogenic insult to the genome “hard wires” leukaemia stem cells, either through development or at some stage, to one cell lineage. Unlike normal haematopoietic stem cells, oncogene-transformed leukaemia stem cells and their progeny are unable to adopt an alternative pathway.
Lineage (genetic)
Cite
Citations (2)
Cite
Citations (361)
Cite
Citations (759)
This chapter discusses the role of (mostly canonical) Wnt signaling in adult stem cells, beginning with intestinal stem cells, as for this tissue most is known about the role of Wnt signaling in self-renewal, differentiation, and quiescence. Another tissue that displays rapid turnover, the skin, also contains stem cells that are dependent on Wnt signaling. Compared to the convincing studies on the role of Wnt signaling in adult stem cells in skin and gut, a role for Wnt in adult HSCs (the prototypical adult stem cell) has proven much more difficult to demonstrate. Although the strength of its signals in HSCs is possibly lower than in other adult stem cell systems, the Wnt pathway is likely to play an important role in the self-renewal program in hematopoiesis.
Hematopoietic stem cell
Cite
Citations (0)
Multipotent Stem Cell
Blood cell
Cite
Citations (668)
Dysregulation of WNT signaling has been reported in many malignancies.This study was conducted to investigate the expression pattern of 14 members of the WNT gene family in different immunophenotypic subtypes of ALL.Semi-quantitative RT-PCR was performed on samples from 71 ALL patients and 36 age-matched healthy individuals. The ALL patients were categorized into B-ALL (76%), T-ALL (22.6%) and mixed lineage (1.4%) and the B-ALL cases were further classified into pro-B, pre-BI, pre-BII and immature/mature-B based on immuno-phenotypic results.Among the WNT genes, WNT-7B (p=0.026), WNT-9A (p=0.020) and WNT-16B (p=0.023) were significantly over-expressed, whereas WNT-2B (p=0.033), WNT-5A (p=0.016), WNT-7A (p<0.0001) and WNT-10A (p<0.0001) were down-regulated in B-ALL. Among the T-ALL subtype, however, significant down-regulation of WNT-2B, WNT-5B, WNT-7A, WNT-10A and WNT-11 was evident. Comparison between B-ALL subtypes showed significant over-expression of WNT-7B, WNT-9A and WNT-5B in certain subtypes.Our results suggest contribution of the WNT genes in leukemogenesis of ALL.
LRP5
LRP6
Cite
Citations (4)