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Stem cell factor (SCF) and KIT signaling are not necessary for early mast cell development, according to research published in Blood.
It has been assumed that the differentiation of hematopoietic progenitors to mast cells requires SCF and KIT signaling.
However, researchers found that mast cell progenitors can survive, mature, and proliferate in the absence of SCF and KIT signaling.
The researchers began this work by analyzing mast cell progenitor populations in samples from healthy subjects, patients with chronic myeloid leukemia (CML) or gastrointestinal stromal tumors (GIST) who were treated with imatinib, and patients with systemic mastocytosis carrying the D816V KIT mutation.
Imatinib inhibits KIT signaling, and the D816V KIT mutation causes KIT signaling to be constitutively active.
The researchers found the imatinib-treated CML and GIST patients and the patients with systemic mastocytosis all had mast cell progenitor populations similar to those observed in healthy subjects.
The team therefore concluded that dysfunctional KIT signaling does not affect the frequency of circulating mast cell progenitors in vivo.
On the other hand, the researchers also found that circulating mast cells were sensitive to imatinib in patients with CML. The patients had higher numbers of peripheral blood mast cells at diagnosis than they did after treatment with imatinib.
“When the patients were treated with the drug imatinib, which blocks the effect of stem cell factor, the number of mature mast cells dropped, while the number of progenitor cells did not change,” said study author Gunnar Nilsson, PhD, of Karolinska Institutet in Stockholm, Sweden.
Subsequent experiments showed that mast cell progenitors can survive in vitro without KIT signaling and without SCF. In addition, mast cell progenitors were able to mature and proliferate in vitro without SCF.
In fact, the researchers said they found that interleukin 3 was sufficient to promote the survival of mast cell progenitors in vitro.
“The study increases our understanding of how mast cells are formed and could be important in the development of new therapies, for example, for mastocytosis . . . ,” said study author Joakim Dahlin, PhD, of the University of Cambridge in the UK.
“One hypothesis that we will now test is whether interleukin 3 can be a new target in the treatment of mast cell-driven diseases.” 
Stem cell factor (SCF) and KIT signaling are not necessary for early mast cell development, according to research published in Blood.
It has been assumed that the differentiation of hematopoietic progenitors to mast cells requires SCF and KIT signaling.
However, researchers found that mast cell progenitors can survive, mature, and proliferate in the absence of SCF and KIT signaling.
The researchers began this work by analyzing mast cell progenitor populations in samples from healthy subjects, patients with chronic myeloid leukemia (CML) or gastrointestinal stromal tumors (GIST) who were treated with imatinib, and patients with systemic mastocytosis carrying the D816V KIT mutation.
Imatinib inhibits KIT signaling, and the D816V KIT mutation causes KIT signaling to be constitutively active.
The researchers found the imatinib-treated CML and GIST patients and the patients with systemic mastocytosis all had mast cell progenitor populations similar to those observed in healthy subjects.
The team therefore concluded that dysfunctional KIT signaling does not affect the frequency of circulating mast cell progenitors in vivo.
On the other hand, the researchers also found that circulating mast cells were sensitive to imatinib in patients with CML. The patients had higher numbers of peripheral blood mast cells at diagnosis than they did after treatment with imatinib.
“When the patients were treated with the drug imatinib, which blocks the effect of stem cell factor, the number of mature mast cells dropped, while the number of progenitor cells did not change,” said study author Gunnar Nilsson, PhD, of Karolinska Institutet in Stockholm, Sweden.
Subsequent experiments showed that mast cell progenitors can survive in vitro without KIT signaling and without SCF. In addition, mast cell progenitors were able to mature and proliferate in vitro without SCF.
In fact, the researchers said they found that interleukin 3 was sufficient to promote the survival of mast cell progenitors in vitro.
“The study increases our understanding of how mast cells are formed and could be important in the development of new therapies, for example, for mastocytosis . . . ,” said study author Joakim Dahlin, PhD, of the University of Cambridge in the UK.
“One hypothesis that we will now test is whether interleukin 3 can be a new target in the treatment of mast cell-driven diseases.”
Stem cell factor (SCF) and KIT signaling are not necessary for early mast cell development, according to research published in Blood.
It has been assumed that the differentiation of hematopoietic progenitors to mast cells requires SCF and KIT signaling.
However, researchers found that mast cell progenitors can survive, mature, and proliferate in the absence of SCF and KIT signaling.
The researchers began this work by analyzing mast cell progenitor populations in samples from healthy subjects, patients with chronic myeloid leukemia (CML) or gastrointestinal stromal tumors (GIST) who were treated with imatinib, and patients with systemic mastocytosis carrying the D816V KIT mutation.
Imatinib inhibits KIT signaling, and the D816V KIT mutation causes KIT signaling to be constitutively active.
The researchers found the imatinib-treated CML and GIST patients and the patients with systemic mastocytosis all had mast cell progenitor populations similar to those observed in healthy subjects.
The team therefore concluded that dysfunctional KIT signaling does not affect the frequency of circulating mast cell progenitors in vivo.
On the other hand, the researchers also found that circulating mast cells were sensitive to imatinib in patients with CML. The patients had higher numbers of peripheral blood mast cells at diagnosis than they did after treatment with imatinib.
“When the patients were treated with the drug imatinib, which blocks the effect of stem cell factor, the number of mature mast cells dropped, while the number of progenitor cells did not change,” said study author Gunnar Nilsson, PhD, of Karolinska Institutet in Stockholm, Sweden.
Subsequent experiments showed that mast cell progenitors can survive in vitro without KIT signaling and without SCF. In addition, mast cell progenitors were able to mature and proliferate in vitro without SCF.
In fact, the researchers said they found that interleukin 3 was sufficient to promote the survival of mast cell progenitors in vitro.
“The study increases our understanding of how mast cells are formed and could be important in the development of new therapies, for example, for mastocytosis . . . ,” said study author Joakim Dahlin, PhD, of the University of Cambridge in the UK.
“One hypothesis that we will now test is whether interleukin 3 can be a new target in the treatment of mast cell-driven diseases.”