In a letter to the editor of Leukemia, researchers reported that the engraftment of bone marrow cells from patients with indolent systemic mastocytosis into NOD-SCID-IL-2Rγ−/− (NSG) mice expressing human membrane-bound stem cell factor (NSGSCF mice) correlated with the World Health Organization (WHO) category and prognosis of their disease. 

Systemic mastocytosis is characterized by the abnormal growth and accumulation of mast cells throughout the body. The WHO classifies the disease into nonadvanced forms (indolent/smoldering systemic mastocytosis) and advanced forms (aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia). 

It is, however, clinically challenging to predict prognosis, given that risk parameters are unreliable. For example, while high tryptase levels may point to a poorer prognosis, they may also be increased in the absence of disease progression. As a result, clinicians have proposed measuring the number and disease-propagating capacity of neoplastic stem cells in patients with systemic mastocytosis. 

Scientists have identified leukemic stem cells in patients with systemic mastocytosis; in most cases, leukemic stem cells have been found to produce detectable engraftment in NSGSCF mice. The researchers sought to “demonstrate a definite correlation between the WHO category of [systemic mastocytosis] and the engraftment levels produced by neoplastic stem cells in NSGSCF mice.” 

Read more about systemic mastocytosis etiology

They obtained 3 bone marrow aspirate samples from patients with indolent systemic mastocytosis, which were then injected into NSGSCF mice. The mice were monitored daily and were euthanized when they demonstrated disease symptoms or at the end of the 52-week study period, when bone marrow cells were then extracted.

Although flow cytometry assessments did not detect any engraftment of human cells in the mice, immunohistochemistry detected some human CD45+ cells engrafting the bone marrow in most mice examined. This differs from previous studies conducted using bone marrow samples from patients with advanced systemic mastocytosis in which engraftment was detectable via flow cytometry. 

“All in all, our data suggest that the aggressiveness of [systemic mastocytosis] correlates with the WHO type and with engraftment rates produced by neoplastic stem cells in NSGSCF mice,” the authors concluded. 


Willmann M, Peter B, Slavnitsch K, et al. Engraftment in NSGSCF mice correlates with the WHO category and prognosis in systemic mastocytosisLeukemia. Published online March 14, 2023. doi:10.1038/s41375-023-01871-7