User login
Researchers say they’ve created the first animal model that recapitulates the predisposition to cancer observed in patients with Diamond-Blackfan anemia (DBA).
DBA is caused by mutations in ribosomal genes such as RPL11, so the researchers set out to determine the effects of manipulating RPL11 in mice.
The team found that RPL11-deficient mice
developed anemia, but they also had impaired p53 responses, elevated cMYC levels, and increased susceptibility to radiation-induced lymphomagenesis.
Manuel Serrano, PhD, of Centro Nacional de Investigaciones Oncologicas (CNIO) in Madrid, Spain, and his colleagues described these findings in Cell Reports.
Previous observational studies suggested that around 20% of patients with DBA develop cancers, particularly lymphomas. Other research groups have developed animal models that recapitulate certain characteristics of DBA but not the predisposition to cancer.
In an attempt to change that, Dr Serrano and his colleagues focused their work on RPL11.
“Cells need the ribosomes to function properly in order to proliferate and grow,” Dr Serrano explained. “We knew that when something goes wrong in these organelles, RPL11 operates as a switch that activates the p53 gene to stop the cells from proliferating and forming tumors. This mechanism is called ribosomal stress.”
“P53 is one of the main tumor suppressor genes identified to date, to the extent that its relevance in preventing cancer has led to it being named the ‘guardian of the genome.’ This important function made us think that the protein could play a crucial role in the cancer predisposition observed in patients with DBA. If RPL11 is mutated, it loses the ability to activate p53 to prevent tumors caused by cellular damage.”
In fact, the researchers found that total or partial deletion of RPL11 impairs the normal function of p53 and increases levels of cMYC, which can promote tumor development.
“We believe that, in DBA, both factors combined contribute to induce the development of cancer,” said Lucía Morgado-Palacín, also of CNIO.
The researchers’ experiments supported this idea, as mice with heterozygous RPL11 deletion exhibited increased susceptibility to radiation-induced lymphomagenesis.
Mice with heterozygous RPL11 deletion also developed anemia that was associated with decreased erythroid
progenitors and defective erythroid maturation.
Homozygous deletion of RPL11, on the other hand, led to bone marrow aplasia
and intestinal atrophy in adult mice. And these mice died within a few weeks. 
Researchers say they’ve created the first animal model that recapitulates the predisposition to cancer observed in patients with Diamond-Blackfan anemia (DBA).
DBA is caused by mutations in ribosomal genes such as RPL11, so the researchers set out to determine the effects of manipulating RPL11 in mice.
The team found that RPL11-deficient mice
developed anemia, but they also had impaired p53 responses, elevated cMYC levels, and increased susceptibility to radiation-induced lymphomagenesis.
Manuel Serrano, PhD, of Centro Nacional de Investigaciones Oncologicas (CNIO) in Madrid, Spain, and his colleagues described these findings in Cell Reports.
Previous observational studies suggested that around 20% of patients with DBA develop cancers, particularly lymphomas. Other research groups have developed animal models that recapitulate certain characteristics of DBA but not the predisposition to cancer.
In an attempt to change that, Dr Serrano and his colleagues focused their work on RPL11.
“Cells need the ribosomes to function properly in order to proliferate and grow,” Dr Serrano explained. “We knew that when something goes wrong in these organelles, RPL11 operates as a switch that activates the p53 gene to stop the cells from proliferating and forming tumors. This mechanism is called ribosomal stress.”
“P53 is one of the main tumor suppressor genes identified to date, to the extent that its relevance in preventing cancer has led to it being named the ‘guardian of the genome.’ This important function made us think that the protein could play a crucial role in the cancer predisposition observed in patients with DBA. If RPL11 is mutated, it loses the ability to activate p53 to prevent tumors caused by cellular damage.”
In fact, the researchers found that total or partial deletion of RPL11 impairs the normal function of p53 and increases levels of cMYC, which can promote tumor development.
“We believe that, in DBA, both factors combined contribute to induce the development of cancer,” said Lucía Morgado-Palacín, also of CNIO.
The researchers’ experiments supported this idea, as mice with heterozygous RPL11 deletion exhibited increased susceptibility to radiation-induced lymphomagenesis.
Mice with heterozygous RPL11 deletion also developed anemia that was associated with decreased erythroid
progenitors and defective erythroid maturation.
Homozygous deletion of RPL11, on the other hand, led to bone marrow aplasia
and intestinal atrophy in adult mice. And these mice died within a few weeks.
Researchers say they’ve created the first animal model that recapitulates the predisposition to cancer observed in patients with Diamond-Blackfan anemia (DBA).
DBA is caused by mutations in ribosomal genes such as RPL11, so the researchers set out to determine the effects of manipulating RPL11 in mice.
The team found that RPL11-deficient mice
developed anemia, but they also had impaired p53 responses, elevated cMYC levels, and increased susceptibility to radiation-induced lymphomagenesis.
Manuel Serrano, PhD, of Centro Nacional de Investigaciones Oncologicas (CNIO) in Madrid, Spain, and his colleagues described these findings in Cell Reports.
Previous observational studies suggested that around 20% of patients with DBA develop cancers, particularly lymphomas. Other research groups have developed animal models that recapitulate certain characteristics of DBA but not the predisposition to cancer.
In an attempt to change that, Dr Serrano and his colleagues focused their work on RPL11.
“Cells need the ribosomes to function properly in order to proliferate and grow,” Dr Serrano explained. “We knew that when something goes wrong in these organelles, RPL11 operates as a switch that activates the p53 gene to stop the cells from proliferating and forming tumors. This mechanism is called ribosomal stress.”
“P53 is one of the main tumor suppressor genes identified to date, to the extent that its relevance in preventing cancer has led to it being named the ‘guardian of the genome.’ This important function made us think that the protein could play a crucial role in the cancer predisposition observed in patients with DBA. If RPL11 is mutated, it loses the ability to activate p53 to prevent tumors caused by cellular damage.”
In fact, the researchers found that total or partial deletion of RPL11 impairs the normal function of p53 and increases levels of cMYC, which can promote tumor development.
“We believe that, in DBA, both factors combined contribute to induce the development of cancer,” said Lucía Morgado-Palacín, also of CNIO.
The researchers’ experiments supported this idea, as mice with heterozygous RPL11 deletion exhibited increased susceptibility to radiation-induced lymphomagenesis.
Mice with heterozygous RPL11 deletion also developed anemia that was associated with decreased erythroid
progenitors and defective erythroid maturation.
Homozygous deletion of RPL11, on the other hand, led to bone marrow aplasia
and intestinal atrophy in adult mice. And these mice died within a few weeks.