Mastocytosis in adults often presents with skin lesions. A bone marrow biopsy (BMB) is necessary to confirm or exclude the presence of systemic mastocytosis (SM) in these cases. When a BMB is not performed the provisional diagnosis is mastocytosis in the skin (MIS). No generally accepted scoring system has been established to estimate the risk of SM in these patients. To develop a risk score to predict SM in adults with MIS. We examined 1145 patients with MIS from the European Competence Network on Mastocytosis (ECNM) registry who underwent a BMB. 944 patients had SM and 201 patients had cutaneous mastocytosis (CM); 63.7% were female, 36.3% were male. Median age was 44±13.3 years. The median serum tryptase level amounted to 29.3±81.9 ng/ml. We established a multivariate regression model using the whole population of patients as a training and validation set (bootstrapping). A risk score was developed and validated with receiver operating curves. In the multivariate model, the tryptase level (p<0.001), constitutional/cardiovascular symptoms (p=0.014) and bone symptoms/osteoporosis (p<0.001) were independent predictors of SM (p<0.001, sensitivity 90.7%, specificity 69.1%). A 6-point risk score was established (risk, 10.7-98.0%) and validated. Using a large dataset of the ECNM registry we created a risk score to predict the presence of SM in patients with MIS. Although the score will need further validation in independent cohorts, our score seems to discriminate safely between patients with SM and with pure CM.

Advanced systemic mastocytosis is a relatively rare entity where allogeneic stem cell transplantation can lead to the cure of the disease in selected patients. Delayed incomplete responses with graft-versus-mastocytosis effect were published in a few cases. In this particular patient's report, we describe the direct evidence and potency of graft-versus-mastocytosis effect of donor lymphocyte infusions in a patient with systemic mastocytosis with associated hematological neoplasm (SM-AHN). In a 53-year-old female patient, an allogeneic stem cell transplantation after conventional induction treatment was performed for transformed acute myeloid leukemia (AML) during the course of polycythemia vera. After 6 years of remission period of AML and PV, the patient developed aleukemic mast cell leukemia and JAK2-positive myeloproliferative neoplasm (SM-AHN). We were able to achieve a sustained complete remission of SM-AHN lasting for 6 years with only donor lymphocyte infusions in a status of mixed chimerism. The patient is in a good clinical condition and remission. The potent graft-versus-mastocytosis effect in this patient resembles the favorable effect of donor lymphocyte infusions in relapsing chronic myeloid leukemia patients after transplantation. This patient is, to our knowledge, the first case showing the proof of principle of graft-versus-mastocytosis effect.

Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell (HSC)-originated diseases with clonal myeloproliferation. The constitutive activation of the JAK/STAT pathway is frequently detected in patients with Philadelphia chromosome-negative (Ph^–) MPNs with an acquired JAK2V617F mutation. The c-MYC proto-oncogene is associated with malignant growth and cellular transformation, and JAK2V617F was previously shown to induce constitutive expression of c-MYC. This study examines the expressional profile of c-MYC in Ph^– MPNs with JAK2V617F and highlights its hierarchical level of activation in circulating hematopoietic stem/progenitor cell (HSPC) subgroups. Mononuclear cells (MNCs) of Ph^– MPNs were fluorochrome-labeled in situ with wild-type (wt) JAK2 or JAK2V617F mRNA gold nanoparticle technology and sorted simultaneously. Isolated populations of JAK2wt or JAK2V617F were evaluated for their c-MYC expressions. The MNCs of 14 Ph^– MPNs were further isolated for the study of HSPC subgroups regarding their CD34 and CD133 expressions, evaluated for the presence of JAK2V617F, and compared to cord blood (CB) counterparts for the expression of c-MYC. The mRNA-labeled gold nanoparticle-treated MNCs were determined to have the highest ratio of c-MYC relative fold-change expression in the biallelic JAK2V617F compartment compared to JAK2wt. The relative c-MYC expression in MNCs of MPNs was significantly increased compared to CB (p=0.01). The circulating HSPCs of CD133^+/–CD34⁻ MPNs had statistically significantly elevated c-MYC expression compared to CB. This is the first study of circulating CD133^+/–CD34⁻ cells in Ph^– MPNs and it has revealed elevated c-MYC expression levels in HSCs/endothelial progenitor cells (HSCs/EPCs) and EPCs. Furthermore, the steady increase in the expression of c-MYC within MNCs carrying no mutations and monoallelic or biallelic JAK2V617F transcripts was notable. The presence of JAK2V617F with respect to c-MYC expression in the circulating HSCs/EPCs and EPCs of MPNs might provide some evidence for the initiation of JAK2V617F and propagation of disease. Further studies are needed to clarify the implications of increased c-MYC expression in such populations.