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Preclinical research suggests bacterial signals are crucial to the development of pre-leukemic myeloproliferation (PMP).
Researchers found that bacterial translocation leads to increased production of interleukin-6 (IL-6), which prompts PMP development in mice with Tet2 deficiency.
However, antibiotics and blockade of IL-6 were able to reverse PMP in the mice.
Bana Jabri, MD, PhD, of the University of Chicago in Illinois, and her colleagues reported these findings in Nature.
The researchers noted that, in humans and mice, TET2 deficiency leads to increased self-renewal of hematopoietic stem cells favoring the myeloid lineage, and this can lead to PMP.
However, not all humans or mice with TET2 deficiency actually develop PMP, which suggests other factors are at play.
With this in mind, the researchers studied Tet2-deficient mice. The team found that loss of Tet2 expression leads to defects in the intestinal barrier, although it isn’t clear how this occurs.
The intestinal defects allow bacteria living in the gut to spread into the blood and peripheral organs. The spread of bacteria prompts an increase in IL-6. This promotes proliferation of granulocyte–macrophage progenitors that express high levels of IL-6Rα in the absence of Tet2, and this leads to PMP.
The researchers found they could induce PMP in symptom-free Tet2−/− mice by disrupting intestinal barrier integrity. PMP also developed in response to systemic bacterial stimuli.
However, antibiotics and blockade of IL-6 signals could reverse PMP in mice that developed symptoms. And germ-free Tet2−/− mice did not develop symptoms, which supports the idea that bacteria must be present to drive the development of PMP.
Dr Jabri said the next step is to conduct studies in humans to see if patients with PMP also have signs of bacterial translocation. Then, clinical trials could test whether treatments that target aberrant IL-6 signals in response to bacteria can reverse the course of PMP.
Preclinical research suggests bacterial signals are crucial to the development of pre-leukemic myeloproliferation (PMP).
Researchers found that bacterial translocation leads to increased production of interleukin-6 (IL-6), which prompts PMP development in mice with Tet2 deficiency.
However, antibiotics and blockade of IL-6 were able to reverse PMP in the mice.
Bana Jabri, MD, PhD, of the University of Chicago in Illinois, and her colleagues reported these findings in Nature.
The researchers noted that, in humans and mice, TET2 deficiency leads to increased self-renewal of hematopoietic stem cells favoring the myeloid lineage, and this can lead to PMP.
However, not all humans or mice with TET2 deficiency actually develop PMP, which suggests other factors are at play.
With this in mind, the researchers studied Tet2-deficient mice. The team found that loss of Tet2 expression leads to defects in the intestinal barrier, although it isn’t clear how this occurs.
The intestinal defects allow bacteria living in the gut to spread into the blood and peripheral organs. The spread of bacteria prompts an increase in IL-6. This promotes proliferation of granulocyte–macrophage progenitors that express high levels of IL-6Rα in the absence of Tet2, and this leads to PMP.
The researchers found they could induce PMP in symptom-free Tet2−/− mice by disrupting intestinal barrier integrity. PMP also developed in response to systemic bacterial stimuli.
However, antibiotics and blockade of IL-6 signals could reverse PMP in mice that developed symptoms. And germ-free Tet2−/− mice did not develop symptoms, which supports the idea that bacteria must be present to drive the development of PMP.
Dr Jabri said the next step is to conduct studies in humans to see if patients with PMP also have signs of bacterial translocation. Then, clinical trials could test whether treatments that target aberrant IL-6 signals in response to bacteria can reverse the course of PMP.
Preclinical research suggests bacterial signals are crucial to the development of pre-leukemic myeloproliferation (PMP).
Researchers found that bacterial translocation leads to increased production of interleukin-6 (IL-6), which prompts PMP development in mice with Tet2 deficiency.
However, antibiotics and blockade of IL-6 were able to reverse PMP in the mice.
Bana Jabri, MD, PhD, of the University of Chicago in Illinois, and her colleagues reported these findings in Nature.
The researchers noted that, in humans and mice, TET2 deficiency leads to increased self-renewal of hematopoietic stem cells favoring the myeloid lineage, and this can lead to PMP.
However, not all humans or mice with TET2 deficiency actually develop PMP, which suggests other factors are at play.
With this in mind, the researchers studied Tet2-deficient mice. The team found that loss of Tet2 expression leads to defects in the intestinal barrier, although it isn’t clear how this occurs.
The intestinal defects allow bacteria living in the gut to spread into the blood and peripheral organs. The spread of bacteria prompts an increase in IL-6. This promotes proliferation of granulocyte–macrophage progenitors that express high levels of IL-6Rα in the absence of Tet2, and this leads to PMP.
The researchers found they could induce PMP in symptom-free Tet2−/− mice by disrupting intestinal barrier integrity. PMP also developed in response to systemic bacterial stimuli.
However, antibiotics and blockade of IL-6 signals could reverse PMP in mice that developed symptoms. And germ-free Tet2−/− mice did not develop symptoms, which supports the idea that bacteria must be present to drive the development of PMP.
Dr Jabri said the next step is to conduct studies in humans to see if patients with PMP also have signs of bacterial translocation. Then, clinical trials could test whether treatments that target aberrant IL-6 signals in response to bacteria can reverse the course of PMP.