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A microRNA-targeting drug could improve the effectiveness of tyrosine kinase inhibitors (TKIs) against chronic myelogenous leukemia (CML), according to preclinical research published in Nature Medicine.
The drug, miristen, targets miR-126, a microRNA expressed in leukemia stem cells (LSCs).
Researchers found that miristen “enhanced the anti-leukemic effects of TKI treatment” in mouse models of CML and “strongly diminished LSC leukemia-initiating capacity.”
“This could be a major breakthrough for people who are in remission for CML because there is always a concern that the disease will come back if TKI treatment is stopped,” said study author Bin Zhang, PhD, of City of Hope Medical Center in Duarte, California.
“Miristen could be the drug that sends the disease into permanent remission.”
For this study, Dr Zhang and her colleagues tested miristen alone and in combination with the TKI nilotinib in mouse models of CML.
The best results were seen in mice treated with miristen and nilotinib. Transplantation of bone marrow cells collected from mice treated with miristen and nilotinib resulted in no sign of leukemia in the healthy recipient mice, meaning all LSCs were eliminated.
The researchers believe miristen simply makes TKIs more effective in killing LSCs. The team also thinks they have discovered the key to the treatment’s success.
The researchers found that endothelial cells in the blood vessels of the bone marrow contain high levels of miR-126. These endothelial cells transfer miR-126 to LSCs, essentially feeding the leukemia what it needs to survive and grow.
The team hypothesized that to eliminate CML, miristen had to lower miR-126 in both the LSCs and the endothelial cells. Testing proved this theory correct.
“What we have discovered is how the microenvironment surrounding the leukemia stem cells supports them and how you need to target miR-126 in the leukemia stem cells and the microenvironment to completely eradicate the disease,” said study author Guido Marcucci, MD, of City of Hope.
“Our current study showed these findings may also apply to other types of leukemia.”
A microRNA-targeting drug could improve the effectiveness of tyrosine kinase inhibitors (TKIs) against chronic myelogenous leukemia (CML), according to preclinical research published in Nature Medicine.
The drug, miristen, targets miR-126, a microRNA expressed in leukemia stem cells (LSCs).
Researchers found that miristen “enhanced the anti-leukemic effects of TKI treatment” in mouse models of CML and “strongly diminished LSC leukemia-initiating capacity.”
“This could be a major breakthrough for people who are in remission for CML because there is always a concern that the disease will come back if TKI treatment is stopped,” said study author Bin Zhang, PhD, of City of Hope Medical Center in Duarte, California.
“Miristen could be the drug that sends the disease into permanent remission.”
For this study, Dr Zhang and her colleagues tested miristen alone and in combination with the TKI nilotinib in mouse models of CML.
The best results were seen in mice treated with miristen and nilotinib. Transplantation of bone marrow cells collected from mice treated with miristen and nilotinib resulted in no sign of leukemia in the healthy recipient mice, meaning all LSCs were eliminated.
The researchers believe miristen simply makes TKIs more effective in killing LSCs. The team also thinks they have discovered the key to the treatment’s success.
The researchers found that endothelial cells in the blood vessels of the bone marrow contain high levels of miR-126. These endothelial cells transfer miR-126 to LSCs, essentially feeding the leukemia what it needs to survive and grow.
The team hypothesized that to eliminate CML, miristen had to lower miR-126 in both the LSCs and the endothelial cells. Testing proved this theory correct.
“What we have discovered is how the microenvironment surrounding the leukemia stem cells supports them and how you need to target miR-126 in the leukemia stem cells and the microenvironment to completely eradicate the disease,” said study author Guido Marcucci, MD, of City of Hope.
“Our current study showed these findings may also apply to other types of leukemia.”
A microRNA-targeting drug could improve the effectiveness of tyrosine kinase inhibitors (TKIs) against chronic myelogenous leukemia (CML), according to preclinical research published in Nature Medicine.
The drug, miristen, targets miR-126, a microRNA expressed in leukemia stem cells (LSCs).
Researchers found that miristen “enhanced the anti-leukemic effects of TKI treatment” in mouse models of CML and “strongly diminished LSC leukemia-initiating capacity.”
“This could be a major breakthrough for people who are in remission for CML because there is always a concern that the disease will come back if TKI treatment is stopped,” said study author Bin Zhang, PhD, of City of Hope Medical Center in Duarte, California.
“Miristen could be the drug that sends the disease into permanent remission.”
For this study, Dr Zhang and her colleagues tested miristen alone and in combination with the TKI nilotinib in mouse models of CML.
The best results were seen in mice treated with miristen and nilotinib. Transplantation of bone marrow cells collected from mice treated with miristen and nilotinib resulted in no sign of leukemia in the healthy recipient mice, meaning all LSCs were eliminated.
The researchers believe miristen simply makes TKIs more effective in killing LSCs. The team also thinks they have discovered the key to the treatment’s success.
The researchers found that endothelial cells in the blood vessels of the bone marrow contain high levels of miR-126. These endothelial cells transfer miR-126 to LSCs, essentially feeding the leukemia what it needs to survive and grow.
The team hypothesized that to eliminate CML, miristen had to lower miR-126 in both the LSCs and the endothelial cells. Testing proved this theory correct.
“What we have discovered is how the microenvironment surrounding the leukemia stem cells supports them and how you need to target miR-126 in the leukemia stem cells and the microenvironment to completely eradicate the disease,” said study author Guido Marcucci, MD, of City of Hope.
“Our current study showed these findings may also apply to other types of leukemia.”