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Positive Regulator Molecules

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.

Positive Regulator Molecules

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To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.

Inhibition of Cdk Activity

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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...

M-Cdk Drives Transition Into Mitosis

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Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...

The Cell Cycle Control System

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The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...

Abnormal Proliferation

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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...

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Cyclin D1 expression in peripheral T-cell lymphomas.

Joo Y Song¹, Liping Song¹, Alex F Herrera²

¹Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA.

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc

|July 30, 2016

Summary

This summary is machine-generated.

Cyclin D1 overexpression, typically seen in B-cell lymphomas, is also found in some T-cell lymphomas, particularly ALK+ anaplastic large cell lymphoma. This finding suggests cyclin D1 may be a therapeutic target in T-cell lymphomas.

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Area of Science:

Oncology
Cell Biology
Hematopathology

Background:

Cyclin D1 is a key cell cycle regulator, frequently overexpressed in B-cell neoplasms like mantle cell lymphoma.
Expression patterns of cyclin D1 in T-cell lymphomas are not well-characterized.
Targeting cyclin-dependent kinase pathways is a focus for novel cancer therapies.

Purpose of the Study:

To investigate the expression of cyclin D1 in a diverse cohort of peripheral T-cell lymphomas.
To determine if cyclin D1 overexpression in T-cell lymphomas could represent a therapeutic target.
To correlate cyclin D1 expression with genetic alterations (IGH/CCND1 translocation or gene amplification).

Main Methods:

Immunohistochemistry for cyclin D1 protein (SP4 clone) on 200 paraffin-embedded peripheral T-cell lymphoma tissues.
Fluorescence in situ hybridization (FISH) for IGH/CCND1 translocation and CCND1 gene amplification in a subset of cases.
Classification of T-cell lymphomas included ALK+ ALCL, ALK- ALCL, PTCL-NOS, AITL, ENKTCL, EATL, HSTCL, CTCL, and LGLL.

Main Results:

Cyclin D1 overexpression was detected in 8/34 (24%) ALK+ ALCL and 3/44 (7%) ALK- ALCL cases.
Three cases (4%) of PTCL-NOS also showed cyclin D1 positivity.
All other T-cell lymphoma subtypes were negative for cyclin D1. FISH analysis was negative for IGH/CCND1 translocation or extra copies in positive cases.

Conclusions:

Cyclin D1 overexpression is not exclusive to B-cell lymphomas and occurs in a subset of peripheral T-cell lymphomas, notably ALK+ anaplastic large cell lymphoma.
The observed cyclin D1 overexpression in T-cell lymphomas may result from post-translational modifications rather than genetic alterations.
Cyclin D1 represents a potential therapeutic target in specific T-cell lymphomas, particularly ALK+ ALCL, for which cyclin-dependent kinase pathway inhibitors could be beneficial.