Normal and Malignant Hematopoiesis

Shah, Bijal; Zuckerman, Kenneth S.

doi:10.1002/9781444394016.ch1

Cited by 4 publications

(4 citation statements)

References 159 publications

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“…One key downstream pathway is the Wnt/β-catenin pathway, which is involved in both primary mixed-lineage leukaemia development [45] , [49] , [50] and drug resistance [70] , [71] . Whilst the bone marrow niche is the primary provider of extracellular Wnt signals required for both haematopoietic stem cell and leukaemic stem cell self-renewal [51] , [72] , [73] , [74] , MLL1 and MLL-FPs play critical roles in intracellular regulation of Wnt signalling [52] , [75] , [76] , [77] . Therefore, the Mll1-dependent impact of the Cks1/Cks2 axis on Wnt signalling is of particular interest.…”

Section: Discussionmentioning

confidence: 99%

The Cks1/Cks2 axis fine-tunes Mll1 expression and is crucial for MLL-rearranged leukaemia cell viability

Grey

Ivey

Milne

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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The Cdc28 protein kinase subunits, Cks1 and Cks2, play dual roles in Cdk-substrate specificity and Cdk-independent protein degradation, in concert with the E3 ubiquitin ligase complexes SCFSkp2 and APCCdc20. Notable targets controlled by Cks include p27 and Cyclin A. Here, we demonstrate that Cks1 and Cks2 proteins interact with both the MllN and MllC subunits of Mll1 (Mixed-lineage leukaemia 1), and together, the Cks proteins define Mll1 levels throughout the cell cycle. Overexpression of CKS1B and CKS2 is observed in multiple human cancers, including various MLL-rearranged (MLLr) AML subtypes. To explore the importance of MLL-Fusion Protein regulation by CKS1/2, we used small molecule inhibitors (MLN4924 and C1) to modulate their protein degradation functions. These inhibitors specifically reduced the proliferation of MLLr cell lines compared to primary controls. Altogether, this study uncovers a novel regulatory pathway for MLL1, which may open a new therapeutic approach to MLLr leukaemia.

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Section: Discussionmentioning

confidence: 99%

The Cks1/Cks2 axis fine-tunes Mll1 expression and is crucial for MLL-rearranged leukaemia cell viability

Grey

Ivey

Milne

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…The interferon family comprises of IFN-α, IFNγ-R1/2, and IL10-R1/2 receptors whereas, tyrosine kinase receptors consist of FMSlike Tyrosine kinase 3 (FLT3) and c-Kit receptor [25].…”

Section: Role Of Transcription Factors In Hematopoiesismentioning

confidence: 99%

Hematopoietic Stem Cell Molecular Targets and Factors Essential for Hematopoiesis

Raghav¹,

Gangenahalli²

2018

J Stem Cell Res Ther

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Hematopoietic Stem Cells (HSCs) gained popularity in the area of medicine because of its remarkable potential to cure an enormous range of human diseases. These stem cells are used for therapeutic purposes for its regenerative capacity and possessed hematopoiesis. This process reflects characteristic properties, proliferation, and differentiation. These behaviors are a result of protein-mediated molecular interactions. However, these molecular interactions underlying are yet to be explored. Thus, the present review focuses on the molecular basis of hematopoiesis wherein, significant molecular interactions which regulate differentiation and proliferation has been discussed. Primarily, we have addressed the role of cytokines, transcription factors, proliferation, and pathways involved in hematopoiesis. Also, relationship with multiple cytokines, small molecules, nutrients, cell-cell contacts and the extracellular matrix which impel a cascade of signals that controls stem cell behavior and fate has been summarized in this review. A large number of datasets of hematopoiesis is publicly available to researchers around the world. This review also provides databases on hematopoiesis which will be very beneficial in facilitating common analysis, basic research and clinical diagnosis for the treatment of blood-related disorders.

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“…Visto que as células sanguíneas maduras têm vida-média curta, esta função de diferenciação e renovação celular torna-se importantíssima para a manutenção do sistema hematopoiético (7)(8)(9).…”

Section: O Sistema Hematopoiéticounclassified

O envolvimento das glândulas salivares na doença do enxerto contra o hospedeiro: estudo bioquímico e análise proteômica

Antunes¹

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Normal and Malignant Hematopoiesis

Cited by 4 publications

References 159 publications

The Cks1/Cks2 axis fine-tunes Mll1 expression and is crucial for MLL-rearranged leukaemia cell viability

The Cks1/Cks2 axis fine-tunes Mll1 expression and is crucial for MLL-rearranged leukaemia cell viability

Hematopoietic Stem Cell Molecular Targets and Factors Essential for Hematopoiesis

O envolvimento das glândulas salivares na doença do enxerto contra o hospedeiro: estudo bioquímico e análise proteômica

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