Related Experiment Video
Updated: May 8, 2026
09:02
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
Inherited susceptibility to CLL
Helen E Speedy1, Georgina Sava, Richard S Houlston
1Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK.
Advances in Experimental Medicine and Biology
|September 10, 2013
Summary
Genetic predisposition to chronic lymphocytic leukemia (CLL) is complex, involving multiple common low-risk variants rather than a single major gene. Recent studies confirm this polygenic model of inherited susceptibility to CLL.
Area of Science:
- Hematology
- Genetics
- Oncology
Background:
- Chronic lymphocytic leukemia (CLL) is the most prevalent lymphoid malignancy in Western nations, representing approximately 25% of all leukemia cases.
- A significant familial aggregation of CLL exists, with first-degree relatives exhibiting a sevenfold increased risk.
- The precise inherited genetic factors contributing to CLL susceptibility remain largely unidentified.
Purpose of the Study:
- To review the evidence supporting an inherited genetic predisposition to CLL.
- To discuss the currently identified genetic risk loci and their implications for CLL biology.
Main Methods:
- Review of existing genetic studies on CLL families.
- Analysis of recent genome-wide association studies (GWAS) for CLL.
- Integration of findings to understand the genetic architecture of CLL risk.
Main Results:
- Genome-wide association studies have validated a polygenic model for CLL susceptibility.
- Multiple common genetic variants at independent loci have been identified as influencing CLL risk.
- These findings challenge the notion of a single major disease-causing gene for CLL.
Conclusions:
- The inherited genetic basis of CLL is characterized by the co-inheritance of multiple low-risk variants.
- Identified genetic risk loci offer insights into the biological pathways involved in CLL development.
- Understanding these genetic factors is crucial for elucidating the etiology of CLL.
Related Concept Videos
02:21Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
02:59Cancer Prevention
Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
Some...
Some...
02:50Combination Therapies and Personalized Medicine
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:19X-linked Traits
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
01:15Differentiation of Common Myeloid Progenitor Cells
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...