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Investigators say they have identified 9 new risk loci for chronic lymphocytic leukemia (CLL).
The team says the research, published in Nature Communications, provides additional evidence for genetic susceptibility to CLL and sheds new light on the biological basis of CLL development.
They also believe their findings could aid the development of new drugs for CLL or help in selecting existing therapies for CLL
patients.
“We knew people were more likely to develop chronic lymphocytic leukemia if someone in their family had suffered from the disease, but our new research takes a big step towards explaining the underlying genetics,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.
“CLL is essentially a disease of the immune system, and it’s fascinating that so many of the new genetic variants we have uncovered seem to directly affect the behavior of white blood cells and their ability to fight disease. Understanding the genetics of CLL can point us towards new treatments for the disease and help us to use existing targeted drugs more effectively.”
For this study, Dr Houlston and his colleagues analyzed data from 8 studies involving a total of 6200 CLL patients and 17,598 controls.
From this, the team identified 9 CLL risk loci:
- 1p36.11 (rs34676223, P=5.04 × 10−13)
- 1q42.13 (rs41271473, P=1.06 × 10−10)
- 4q24 (rs71597109, P=1.37 × 10−10)
- 4q35.1 (rs57214277, P=3.69 × 10−8)
- 6p21.31 (rs3800461, P=1.97 × 10−8)
- 11q23.2 (rs61904987, P=2.64 × 10−11)
- 18q21.1 (rs1036935, P=3.27 × 10−8)
- 19p13.3 (rs7254272, P=4.67 × 10−8)
- 22q13.33 (rs140522, P=2.70 × 10−9).
The investigators noted that the 4q24 association marked by rs71597109 maps to intron 1 of the gene encoding BANK1 (B-cell scaffold protein with ankyrin repeats 1). BANK1 is only ever activated in B cells and is linked to the autoimmune disease lupus.
The team also pointed out that the 19p13.3 association marked by rs7254272 maps 2.5 kb 5′ to ZBTB7A (zinc finger and BTB domain-containing protein 7a), which is a master regulator of B versus T lymphoid fate. So errors in ZBTB7A could lead to too many B cells in the bloodstream and bone marrow.
And rs140522 maps to 22q13.33, which has been linked to the development of multiple sclerosis. The investigators noted that this region of linkage disequilibrium contains 4 genes. One of them, NCAPH2 (non-SMC condensin II complex subunit H2), is differentially expressed in CLL and normal B cells.
“This fascinating study makes a link between genetic variants in the immune system and the development of leukemia and implicates regions of DNA which are also involved in autoimmune diseases,” said Paul Workman, PhD, chief executive and president of The Institute of Cancer Research, who was not involved in this research.
“The findings could point us towards new ways of treating leukemia or better ways of using existing treatments—potentially including immunotherapies.” 
Investigators say they have identified 9 new risk loci for chronic lymphocytic leukemia (CLL).
The team says the research, published in Nature Communications, provides additional evidence for genetic susceptibility to CLL and sheds new light on the biological basis of CLL development.
They also believe their findings could aid the development of new drugs for CLL or help in selecting existing therapies for CLL
patients.
“We knew people were more likely to develop chronic lymphocytic leukemia if someone in their family had suffered from the disease, but our new research takes a big step towards explaining the underlying genetics,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.
“CLL is essentially a disease of the immune system, and it’s fascinating that so many of the new genetic variants we have uncovered seem to directly affect the behavior of white blood cells and their ability to fight disease. Understanding the genetics of CLL can point us towards new treatments for the disease and help us to use existing targeted drugs more effectively.”
For this study, Dr Houlston and his colleagues analyzed data from 8 studies involving a total of 6200 CLL patients and 17,598 controls.
From this, the team identified 9 CLL risk loci:
- 1p36.11 (rs34676223, P=5.04 × 10−13)
- 1q42.13 (rs41271473, P=1.06 × 10−10)
- 4q24 (rs71597109, P=1.37 × 10−10)
- 4q35.1 (rs57214277, P=3.69 × 10−8)
- 6p21.31 (rs3800461, P=1.97 × 10−8)
- 11q23.2 (rs61904987, P=2.64 × 10−11)
- 18q21.1 (rs1036935, P=3.27 × 10−8)
- 19p13.3 (rs7254272, P=4.67 × 10−8)
- 22q13.33 (rs140522, P=2.70 × 10−9).
The investigators noted that the 4q24 association marked by rs71597109 maps to intron 1 of the gene encoding BANK1 (B-cell scaffold protein with ankyrin repeats 1). BANK1 is only ever activated in B cells and is linked to the autoimmune disease lupus.
The team also pointed out that the 19p13.3 association marked by rs7254272 maps 2.5 kb 5′ to ZBTB7A (zinc finger and BTB domain-containing protein 7a), which is a master regulator of B versus T lymphoid fate. So errors in ZBTB7A could lead to too many B cells in the bloodstream and bone marrow.
And rs140522 maps to 22q13.33, which has been linked to the development of multiple sclerosis. The investigators noted that this region of linkage disequilibrium contains 4 genes. One of them, NCAPH2 (non-SMC condensin II complex subunit H2), is differentially expressed in CLL and normal B cells.
“This fascinating study makes a link between genetic variants in the immune system and the development of leukemia and implicates regions of DNA which are also involved in autoimmune diseases,” said Paul Workman, PhD, chief executive and president of The Institute of Cancer Research, who was not involved in this research.
“The findings could point us towards new ways of treating leukemia or better ways of using existing treatments—potentially including immunotherapies.”
Investigators say they have identified 9 new risk loci for chronic lymphocytic leukemia (CLL).
The team says the research, published in Nature Communications, provides additional evidence for genetic susceptibility to CLL and sheds new light on the biological basis of CLL development.
They also believe their findings could aid the development of new drugs for CLL or help in selecting existing therapies for CLL
patients.
“We knew people were more likely to develop chronic lymphocytic leukemia if someone in their family had suffered from the disease, but our new research takes a big step towards explaining the underlying genetics,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.
“CLL is essentially a disease of the immune system, and it’s fascinating that so many of the new genetic variants we have uncovered seem to directly affect the behavior of white blood cells and their ability to fight disease. Understanding the genetics of CLL can point us towards new treatments for the disease and help us to use existing targeted drugs more effectively.”
For this study, Dr Houlston and his colleagues analyzed data from 8 studies involving a total of 6200 CLL patients and 17,598 controls.
From this, the team identified 9 CLL risk loci:
- 1p36.11 (rs34676223, P=5.04 × 10−13)
- 1q42.13 (rs41271473, P=1.06 × 10−10)
- 4q24 (rs71597109, P=1.37 × 10−10)
- 4q35.1 (rs57214277, P=3.69 × 10−8)
- 6p21.31 (rs3800461, P=1.97 × 10−8)
- 11q23.2 (rs61904987, P=2.64 × 10−11)
- 18q21.1 (rs1036935, P=3.27 × 10−8)
- 19p13.3 (rs7254272, P=4.67 × 10−8)
- 22q13.33 (rs140522, P=2.70 × 10−9).
The investigators noted that the 4q24 association marked by rs71597109 maps to intron 1 of the gene encoding BANK1 (B-cell scaffold protein with ankyrin repeats 1). BANK1 is only ever activated in B cells and is linked to the autoimmune disease lupus.
The team also pointed out that the 19p13.3 association marked by rs7254272 maps 2.5 kb 5′ to ZBTB7A (zinc finger and BTB domain-containing protein 7a), which is a master regulator of B versus T lymphoid fate. So errors in ZBTB7A could lead to too many B cells in the bloodstream and bone marrow.
And rs140522 maps to 22q13.33, which has been linked to the development of multiple sclerosis. The investigators noted that this region of linkage disequilibrium contains 4 genes. One of them, NCAPH2 (non-SMC condensin II complex subunit H2), is differentially expressed in CLL and normal B cells.
“This fascinating study makes a link between genetic variants in the immune system and the development of leukemia and implicates regions of DNA which are also involved in autoimmune diseases,” said Paul Workman, PhD, chief executive and president of The Institute of Cancer Research, who was not involved in this research.
“The findings could point us towards new ways of treating leukemia or better ways of using existing treatments—potentially including immunotherapies.”