Background: Systemic mastocytosis (SM) encompasses a heterogeneous group of clonal disorders characterized by abnormal expansion of mast cells (MCs). Beyond KIT and other genes recurrently mutated in myeloid neoplasms, several genetic variants have been described as predisposing to the development of the disease and influencing its clinical phenotype. Increased copy number variants of the TPSAB1 gene were identified as a cause of nonclonal elevated tryptasemia and defined as hereditary α-tryptasemia (HαT). Moreover, HαT is enriched in patients with SM, where it can affect the incidence of mediator-related symptoms. Objective: In a multicenter data set of 444 patients with MC disorders, we aimed to investigate the clinical correlates of germline TPSAB1 copy number gains. Methods: Droplet digital PCR was performed in all cases to ascertain the presence of HαT. Clinical history along with blood values and bone marrow examination were analyzed. Results: We confirmed a higher incidence of HαT+ cases (n = 59, 13.3%) in patients diagnosed with mastocytosis with respect to the general population (approximately 5%). HαT+ patients were characterized by a lower MC-associated disease burden and higher levels of tryptase. Several disease variables were coherent with this pattern, from bone marrow MC infiltration to MC-related histopathologic traits, which also accounted for a significantly higher incidence of clonal MC activation syndrome in HαT+ (10.2%) compared to HαT- (3.4%, P = .029) patients. We also confirmed that HαT+ carriers had a significantly higher frequency of anaphylaxis, without relevant differences for other clinical manifestations. Conclusion: These findings on a large patient series support and extend previous data, and suggest that knowledge of HαT status may be useful for personalized management of patients with SM.

Disease correlates and clinical relevance of hereditary α-tryptasemia in patients with systemic mastocytosis

Elena, Chiara;Parente, Roberta;Triggiani, Massimo;
2023-01-01

Abstract

Background: Systemic mastocytosis (SM) encompasses a heterogeneous group of clonal disorders characterized by abnormal expansion of mast cells (MCs). Beyond KIT and other genes recurrently mutated in myeloid neoplasms, several genetic variants have been described as predisposing to the development of the disease and influencing its clinical phenotype. Increased copy number variants of the TPSAB1 gene were identified as a cause of nonclonal elevated tryptasemia and defined as hereditary α-tryptasemia (HαT). Moreover, HαT is enriched in patients with SM, where it can affect the incidence of mediator-related symptoms. Objective: In a multicenter data set of 444 patients with MC disorders, we aimed to investigate the clinical correlates of germline TPSAB1 copy number gains. Methods: Droplet digital PCR was performed in all cases to ascertain the presence of HαT. Clinical history along with blood values and bone marrow examination were analyzed. Results: We confirmed a higher incidence of HαT+ cases (n = 59, 13.3%) in patients diagnosed with mastocytosis with respect to the general population (approximately 5%). HαT+ patients were characterized by a lower MC-associated disease burden and higher levels of tryptase. Several disease variables were coherent with this pattern, from bone marrow MC infiltration to MC-related histopathologic traits, which also accounted for a significantly higher incidence of clonal MC activation syndrome in HαT+ (10.2%) compared to HαT- (3.4%, P = .029) patients. We also confirmed that HαT+ carriers had a significantly higher frequency of anaphylaxis, without relevant differences for other clinical manifestations. Conclusion: These findings on a large patient series support and extend previous data, and suggest that knowledge of HαT status may be useful for personalized management of patients with SM.
2023
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11386/4827634
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