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Low doses of the tyrosine kinase inhibitor imatinib can promote hematopoiesis, according to research published in PLOS Pathogens.
Preclinical experiments revealed that the drug can induce differentiation in hematopoietic stem cells (HSCs) and progenitors in the bone marrow,
augment myelopoiesis, and increase the number of myeloid cells in the blood and spleen.
Researchers said these findings suggest imatinib or related drugs could be used to treat infections.
“We think that low doses of imatinib are mimicking ‘emergency hematopoiesis,’ a normal early response to infection,” said study author Daniel Kalman, PhD, of the Emory University School of Medicine in Atlanta, Georgia.
“This was surprising because there are reports that imatinib can be immunosuppressive in some patients. Our data suggest that, at subclinical doses, imatinib can stimulate bone marrow stem cells to produce several types of myeloid cells, such as neutrophils and macrophages, and trigger their exodus from the bone marrow. However, higher doses appear to inhibit this process.”
Dr Kalman and his colleagues observed a 4-fold increase of neutrophils and a 3-fold increase of monocytes in the bone marrow of imatinib-treated mice. However, these mice did not see a significant change in the number of mature B cells, T cells, dendritic cells, eosinophils, or natural killer cells.
Imatinib did not induce the accumulation of HSCs, but it did regulate the accumulation of multipotent progenitors. The drug also reduced the accumulation of HSCs upon infection, which suggests it may increase the flux of HSCs to progenitors.
Imatinib did not increase the number of transplantable HSCs, but it did induce an irreversible commitment of HSCs into progenitors that could differentiate into myeloid cells ex vivo.
Imatinib induced an irreversible differentiation of HSCs or progenitors into myeloid cells in a dose-dependent manner. The drug facilitated the exodus of myeloid cells from the bone marrow only at lower doses. It inhibited this same process at higher doses.
Despite increasing the number of neutrophils, low doses of imatinib did not activate neutrophils. However, the cells retained the capacity to activate upon infection.
In fact, an increase in the number of neutrophils was sufficient to reduce Mycobacterium marinum bacterial load. And imatinib reduced the bacterial load in mice infected with pathogenic Francisella species.
The researchers said these results suggest low doses of imatinib could potentially be used to treat a variety of infections and might prove particularly useful in immunocompromised patients. 
Image by Volker Brinkmann
Low doses of the tyrosine kinase inhibitor imatinib can promote hematopoiesis, according to research published in PLOS Pathogens.
Preclinical experiments revealed that the drug can induce differentiation in hematopoietic stem cells (HSCs) and progenitors in the bone marrow,
augment myelopoiesis, and increase the number of myeloid cells in the blood and spleen.
Researchers said these findings suggest imatinib or related drugs could be used to treat infections.
“We think that low doses of imatinib are mimicking ‘emergency hematopoiesis,’ a normal early response to infection,” said study author Daniel Kalman, PhD, of the Emory University School of Medicine in Atlanta, Georgia.
“This was surprising because there are reports that imatinib can be immunosuppressive in some patients. Our data suggest that, at subclinical doses, imatinib can stimulate bone marrow stem cells to produce several types of myeloid cells, such as neutrophils and macrophages, and trigger their exodus from the bone marrow. However, higher doses appear to inhibit this process.”
Dr Kalman and his colleagues observed a 4-fold increase of neutrophils and a 3-fold increase of monocytes in the bone marrow of imatinib-treated mice. However, these mice did not see a significant change in the number of mature B cells, T cells, dendritic cells, eosinophils, or natural killer cells.
Imatinib did not induce the accumulation of HSCs, but it did regulate the accumulation of multipotent progenitors. The drug also reduced the accumulation of HSCs upon infection, which suggests it may increase the flux of HSCs to progenitors.
Imatinib did not increase the number of transplantable HSCs, but it did induce an irreversible commitment of HSCs into progenitors that could differentiate into myeloid cells ex vivo.
Imatinib induced an irreversible differentiation of HSCs or progenitors into myeloid cells in a dose-dependent manner. The drug facilitated the exodus of myeloid cells from the bone marrow only at lower doses. It inhibited this same process at higher doses.
Despite increasing the number of neutrophils, low doses of imatinib did not activate neutrophils. However, the cells retained the capacity to activate upon infection.
In fact, an increase in the number of neutrophils was sufficient to reduce Mycobacterium marinum bacterial load. And imatinib reduced the bacterial load in mice infected with pathogenic Francisella species.
The researchers said these results suggest low doses of imatinib could potentially be used to treat a variety of infections and might prove particularly useful in immunocompromised patients.
Image by Volker Brinkmann
Low doses of the tyrosine kinase inhibitor imatinib can promote hematopoiesis, according to research published in PLOS Pathogens.
Preclinical experiments revealed that the drug can induce differentiation in hematopoietic stem cells (HSCs) and progenitors in the bone marrow,
augment myelopoiesis, and increase the number of myeloid cells in the blood and spleen.
Researchers said these findings suggest imatinib or related drugs could be used to treat infections.
“We think that low doses of imatinib are mimicking ‘emergency hematopoiesis,’ a normal early response to infection,” said study author Daniel Kalman, PhD, of the Emory University School of Medicine in Atlanta, Georgia.
“This was surprising because there are reports that imatinib can be immunosuppressive in some patients. Our data suggest that, at subclinical doses, imatinib can stimulate bone marrow stem cells to produce several types of myeloid cells, such as neutrophils and macrophages, and trigger their exodus from the bone marrow. However, higher doses appear to inhibit this process.”
Dr Kalman and his colleagues observed a 4-fold increase of neutrophils and a 3-fold increase of monocytes in the bone marrow of imatinib-treated mice. However, these mice did not see a significant change in the number of mature B cells, T cells, dendritic cells, eosinophils, or natural killer cells.
Imatinib did not induce the accumulation of HSCs, but it did regulate the accumulation of multipotent progenitors. The drug also reduced the accumulation of HSCs upon infection, which suggests it may increase the flux of HSCs to progenitors.
Imatinib did not increase the number of transplantable HSCs, but it did induce an irreversible commitment of HSCs into progenitors that could differentiate into myeloid cells ex vivo.
Imatinib induced an irreversible differentiation of HSCs or progenitors into myeloid cells in a dose-dependent manner. The drug facilitated the exodus of myeloid cells from the bone marrow only at lower doses. It inhibited this same process at higher doses.
Despite increasing the number of neutrophils, low doses of imatinib did not activate neutrophils. However, the cells retained the capacity to activate upon infection.
In fact, an increase in the number of neutrophils was sufficient to reduce Mycobacterium marinum bacterial load. And imatinib reduced the bacterial load in mice infected with pathogenic Francisella species.
The researchers said these results suggest low doses of imatinib could potentially be used to treat a variety of infections and might prove particularly useful in immunocompromised patients.