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New research indicates that chronic lymphocytic leukemia (CLL) can develop during nearly any stage of B-cell maturation.
However, CLL that arises from more progressive maturation stages responds better to therapy.
The study also suggests that most methylation events that were previously thought to be tumor-specific are normally present in non-malignant B cells.
These findings were published in Nature Genetics.
Christoph Plass, PhD, of the German Cancer Research Center (DKFZ) in Heidelberg, and his colleagues conducted this study to determine which development stage of B cells marks the origin of B-cell CLL.
The team took blood samples from 268 CLL patients, separated the blood cells using specific B-cell maturation markers and analyzed the methylation patterns of each individual maturation stage.
The investigators were surprised to find that CLL can develop from almost all maturation stages. They also found that maturation was associated with “increasingly favorable clinical outcomes.”
In addition, methylation patterns that were previously regarded as cancer-specific actually reflect the characteristic patterns of the development stages at the moment of cancerous transformation.
The investigators found that the cell “freezes” this methylation pattern, and this is followed by only a few changes that are truly cancer-specific.
The team said they used advanced bioinformatic methods to calculate the small percentage of cancer-specific methylation patterns from the wealth of maturation-related variations.
“Up until recently, it was technically impossible to study the various maturation stages in such detail as we have done,” Dr Plass said. “It took the advanced sequencing technology and the powerful bioinformatic methods that we have available now to make such a detailed comparison possible.”
The investigators said their findings differ from those of prior studies because, with the current study, they compared CLL cells with the whole pool of B-cell maturation stages.
“All differences found were attributed to cancer,” Dr Plass said, adding that some previous works on the cancer epigenome will need to be re-interpreted in the light of the current results.
Next, Dr Plass and his colleagues want to examine other cancer types to determine whether methylation patterns that are thought to be cancer-specific also arise from the normal cellular maturation program. In particular, they plan to study other hematologic malignancies and prostate cancer. 
Photo by Graham Colm
New research indicates that chronic lymphocytic leukemia (CLL) can develop during nearly any stage of B-cell maturation.
However, CLL that arises from more progressive maturation stages responds better to therapy.
The study also suggests that most methylation events that were previously thought to be tumor-specific are normally present in non-malignant B cells.
These findings were published in Nature Genetics.
Christoph Plass, PhD, of the German Cancer Research Center (DKFZ) in Heidelberg, and his colleagues conducted this study to determine which development stage of B cells marks the origin of B-cell CLL.
The team took blood samples from 268 CLL patients, separated the blood cells using specific B-cell maturation markers and analyzed the methylation patterns of each individual maturation stage.
The investigators were surprised to find that CLL can develop from almost all maturation stages. They also found that maturation was associated with “increasingly favorable clinical outcomes.”
In addition, methylation patterns that were previously regarded as cancer-specific actually reflect the characteristic patterns of the development stages at the moment of cancerous transformation.
The investigators found that the cell “freezes” this methylation pattern, and this is followed by only a few changes that are truly cancer-specific.
The team said they used advanced bioinformatic methods to calculate the small percentage of cancer-specific methylation patterns from the wealth of maturation-related variations.
“Up until recently, it was technically impossible to study the various maturation stages in such detail as we have done,” Dr Plass said. “It took the advanced sequencing technology and the powerful bioinformatic methods that we have available now to make such a detailed comparison possible.”
The investigators said their findings differ from those of prior studies because, with the current study, they compared CLL cells with the whole pool of B-cell maturation stages.
“All differences found were attributed to cancer,” Dr Plass said, adding that some previous works on the cancer epigenome will need to be re-interpreted in the light of the current results.
Next, Dr Plass and his colleagues want to examine other cancer types to determine whether methylation patterns that are thought to be cancer-specific also arise from the normal cellular maturation program. In particular, they plan to study other hematologic malignancies and prostate cancer.
Photo by Graham Colm
New research indicates that chronic lymphocytic leukemia (CLL) can develop during nearly any stage of B-cell maturation.
However, CLL that arises from more progressive maturation stages responds better to therapy.
The study also suggests that most methylation events that were previously thought to be tumor-specific are normally present in non-malignant B cells.
These findings were published in Nature Genetics.
Christoph Plass, PhD, of the German Cancer Research Center (DKFZ) in Heidelberg, and his colleagues conducted this study to determine which development stage of B cells marks the origin of B-cell CLL.
The team took blood samples from 268 CLL patients, separated the blood cells using specific B-cell maturation markers and analyzed the methylation patterns of each individual maturation stage.
The investigators were surprised to find that CLL can develop from almost all maturation stages. They also found that maturation was associated with “increasingly favorable clinical outcomes.”
In addition, methylation patterns that were previously regarded as cancer-specific actually reflect the characteristic patterns of the development stages at the moment of cancerous transformation.
The investigators found that the cell “freezes” this methylation pattern, and this is followed by only a few changes that are truly cancer-specific.
The team said they used advanced bioinformatic methods to calculate the small percentage of cancer-specific methylation patterns from the wealth of maturation-related variations.
“Up until recently, it was technically impossible to study the various maturation stages in such detail as we have done,” Dr Plass said. “It took the advanced sequencing technology and the powerful bioinformatic methods that we have available now to make such a detailed comparison possible.”
The investigators said their findings differ from those of prior studies because, with the current study, they compared CLL cells with the whole pool of B-cell maturation stages.
“All differences found were attributed to cancer,” Dr Plass said, adding that some previous works on the cancer epigenome will need to be re-interpreted in the light of the current results.
Next, Dr Plass and his colleagues want to examine other cancer types to determine whether methylation patterns that are thought to be cancer-specific also arise from the normal cellular maturation program. In particular, they plan to study other hematologic malignancies and prostate cancer.