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Tamoxifen, a drug used to treat breast cancer, may be effective against myeloproliferative neoplasms (MPNs) and acute myeloid leukemia (AML) as well, according to research published in Cell Stem Cell.
The study showed that estrogens regulate the survival, proliferation, and self-renewal of stem cells that give rise to MPNs and AML.
Tamoxifen, which targets estrogen receptors, prevented JAK2V617F-induced MPNs in mice and enhanced the effects of chemotherapy against MLL-AF9-induced AML.
“In this study, we demonstrate that tamoxifen has specific effects on certain cells in the bone marrow: the hematopoietic stem cells and their immediate descendants, known as multipotent progenitors,” explained study author Abel Sánchez-Aguilera, PhD, of Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Madrid.
The researchers found that, unlike in breast cancer, where tamoxifen blocks the action of estrogens, in blood cells, the drug acts by imitating the function of the hormone.
Tamoxifen induced apoptosis in short-term hematopoietic stem cells (HSCs) and multipotent progenitors. But in quiescent, long-term HSCs, the drug prompted proliferation and partial loss of function, which was reversible.
Tamoxifen also prevented polycythemia vera-like MPN from developing in mice with HSCs expressing JAK2V617F. The drug prevented MPN-associated neutrophilia and thrombocytosis; alleviated the early increase in red cell counts, hemoglobin, and hematocrit; decreased bone marrow megakaryocytes; and reduced MPN-associated splenomegaly.
Tamoxifen worked by restoring normal levels of apoptosis in mutant cells. It also prompted apoptosis of human JAK2V617F+ hematopoietic stem and progenitor cells (HSPCs) in a xenograft model.
In these models, tamoxifen caused little alteration in the rest of the blood cells, which were maintained at normal levels even after prolonged treatment with the drug.
“Our results suggest that tamoxifen, at a similar dose used for the treatment of other diseases, might be useful to treat myeloproliferative neoplasms at various stages, without being toxic to normal blood cells,” said study author Simón Méndez-Ferrer, PhD, also of CNIC.
In addition, tamoxifen enhanced the effects of conventional chemotherapy on cancerous cells in mice with MLL-AF9-induced AML.
Tamoxifen- and vehicle-treated mice had similar numbers of MLL-AF9+ cells and HSPCs shortly after chemotherapy. But tamoxifen delayed the reappearance of circulating leukemic cells after chemotherapy.
Tamoxifen-treated mice had fewer leukemic cells in the bone marrow, spleen, and blood, although they ultimately died of their disease.
Nevertheless, the researchers concluded that tamoxifen could be a feasible treatment option for patients with MPNs or AML. And the fact that tamoxifen is already approved for clinical use increases the chances of these results leading to a clinical trial. 
Credit: CDC
Tamoxifen, a drug used to treat breast cancer, may be effective against myeloproliferative neoplasms (MPNs) and acute myeloid leukemia (AML) as well, according to research published in Cell Stem Cell.
The study showed that estrogens regulate the survival, proliferation, and self-renewal of stem cells that give rise to MPNs and AML.
Tamoxifen, which targets estrogen receptors, prevented JAK2V617F-induced MPNs in mice and enhanced the effects of chemotherapy against MLL-AF9-induced AML.
“In this study, we demonstrate that tamoxifen has specific effects on certain cells in the bone marrow: the hematopoietic stem cells and their immediate descendants, known as multipotent progenitors,” explained study author Abel Sánchez-Aguilera, PhD, of Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Madrid.
The researchers found that, unlike in breast cancer, where tamoxifen blocks the action of estrogens, in blood cells, the drug acts by imitating the function of the hormone.
Tamoxifen induced apoptosis in short-term hematopoietic stem cells (HSCs) and multipotent progenitors. But in quiescent, long-term HSCs, the drug prompted proliferation and partial loss of function, which was reversible.
Tamoxifen also prevented polycythemia vera-like MPN from developing in mice with HSCs expressing JAK2V617F. The drug prevented MPN-associated neutrophilia and thrombocytosis; alleviated the early increase in red cell counts, hemoglobin, and hematocrit; decreased bone marrow megakaryocytes; and reduced MPN-associated splenomegaly.
Tamoxifen worked by restoring normal levels of apoptosis in mutant cells. It also prompted apoptosis of human JAK2V617F+ hematopoietic stem and progenitor cells (HSPCs) in a xenograft model.
In these models, tamoxifen caused little alteration in the rest of the blood cells, which were maintained at normal levels even after prolonged treatment with the drug.
“Our results suggest that tamoxifen, at a similar dose used for the treatment of other diseases, might be useful to treat myeloproliferative neoplasms at various stages, without being toxic to normal blood cells,” said study author Simón Méndez-Ferrer, PhD, also of CNIC.
In addition, tamoxifen enhanced the effects of conventional chemotherapy on cancerous cells in mice with MLL-AF9-induced AML.
Tamoxifen- and vehicle-treated mice had similar numbers of MLL-AF9+ cells and HSPCs shortly after chemotherapy. But tamoxifen delayed the reappearance of circulating leukemic cells after chemotherapy.
Tamoxifen-treated mice had fewer leukemic cells in the bone marrow, spleen, and blood, although they ultimately died of their disease.
Nevertheless, the researchers concluded that tamoxifen could be a feasible treatment option for patients with MPNs or AML. And the fact that tamoxifen is already approved for clinical use increases the chances of these results leading to a clinical trial.
Credit: CDC
Tamoxifen, a drug used to treat breast cancer, may be effective against myeloproliferative neoplasms (MPNs) and acute myeloid leukemia (AML) as well, according to research published in Cell Stem Cell.
The study showed that estrogens regulate the survival, proliferation, and self-renewal of stem cells that give rise to MPNs and AML.
Tamoxifen, which targets estrogen receptors, prevented JAK2V617F-induced MPNs in mice and enhanced the effects of chemotherapy against MLL-AF9-induced AML.
“In this study, we demonstrate that tamoxifen has specific effects on certain cells in the bone marrow: the hematopoietic stem cells and their immediate descendants, known as multipotent progenitors,” explained study author Abel Sánchez-Aguilera, PhD, of Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Madrid.
The researchers found that, unlike in breast cancer, where tamoxifen blocks the action of estrogens, in blood cells, the drug acts by imitating the function of the hormone.
Tamoxifen induced apoptosis in short-term hematopoietic stem cells (HSCs) and multipotent progenitors. But in quiescent, long-term HSCs, the drug prompted proliferation and partial loss of function, which was reversible.
Tamoxifen also prevented polycythemia vera-like MPN from developing in mice with HSCs expressing JAK2V617F. The drug prevented MPN-associated neutrophilia and thrombocytosis; alleviated the early increase in red cell counts, hemoglobin, and hematocrit; decreased bone marrow megakaryocytes; and reduced MPN-associated splenomegaly.
Tamoxifen worked by restoring normal levels of apoptosis in mutant cells. It also prompted apoptosis of human JAK2V617F+ hematopoietic stem and progenitor cells (HSPCs) in a xenograft model.
In these models, tamoxifen caused little alteration in the rest of the blood cells, which were maintained at normal levels even after prolonged treatment with the drug.
“Our results suggest that tamoxifen, at a similar dose used for the treatment of other diseases, might be useful to treat myeloproliferative neoplasms at various stages, without being toxic to normal blood cells,” said study author Simón Méndez-Ferrer, PhD, also of CNIC.
In addition, tamoxifen enhanced the effects of conventional chemotherapy on cancerous cells in mice with MLL-AF9-induced AML.
Tamoxifen- and vehicle-treated mice had similar numbers of MLL-AF9+ cells and HSPCs shortly after chemotherapy. But tamoxifen delayed the reappearance of circulating leukemic cells after chemotherapy.
Tamoxifen-treated mice had fewer leukemic cells in the bone marrow, spleen, and blood, although they ultimately died of their disease.
Nevertheless, the researchers concluded that tamoxifen could be a feasible treatment option for patients with MPNs or AML. And the fact that tamoxifen is already approved for clinical use increases the chances of these results leading to a clinical trial.