JAK inhibition in a patient with a STAT1 gain-of-function variant reveals STAT1 dysregulation as a common feature of aplastic anemia

Med ◽  
2022 ◽  
Vol 3 (1) ◽  
pp. 42-57.e5
Author(s):  
Jacob M. Rosenberg ◽  
Joshua M. Peters ◽  
Travis Hughes ◽  
Caleb A. Lareau ◽  
Leif S. Ludwig ◽  
...  
2021 ◽  
Author(s):  
Jacob Rosenberg ◽  
Travis Hughes ◽  
Joshua Peters ◽  
Caleb Lareau ◽  
Leif Ludwig ◽  
...  

Abstract An 18-year-old man presented with aplastic anemia, and exome sequencing identified a germline gain-of-function variant in the gene STAT1. Treatment with itacitinib, an investigational selective Janus Kinase 1 (JAK1) inhibitor, resulted in prompt recovery of hematopoiesis. An exhausted CD8+ T cell population and myeloid populations enriched for an interferon-y signature correlated with disease activity. Patient bone marrow sections displayed increased phospho-STAT1 staining, as did other idiopathic aplastic anemia cases, suggesting a shared pathophysiologic mechanism. This study describes the success and mechanism of a molecularly targeted therapy with potential implications for the treatment of aplastic anemias and other autoimmune disorders.


Pneumologie ◽  
2016 ◽  
Vol 70 (10) ◽  
Author(s):  
T Khoury ◽  
R Kuint ◽  
V Molho-Pessach ◽  
Y Ramot ◽  
A Abu Rmeileh ◽  
...  
Keyword(s):  

Author(s):  
Harimohan Garg ◽  
Haritej Anand Khirawari ◽  
Sona Priyadarshi

Background: Pancytopenia is diagnosed when there is a reduction in all three hematopoietic cell lines. Till date there is limited number of studies on the frequency of various causes of pancytopenia. Of these some have been reported from the Indian subcontinent. There appears to be a changing spectrum of pancytopenia over the past two decades. The objective was to study the etiopathological spectrum of adult patients with pancytopenia over a period of one and half year. Methods: The Prospective and retrospective observational study was conducted in the Department of Family Medicine, Batra Hospital and Medical Research Centre, New Delhi.  A total of 120 Patients were included in the study. All patients gave their consent to take part in the study and were subjected to a questionnaire regarding symptoms, past relevant history, lifestyle and detailed clinical examination and investigations as mentioned in materials and methods. Results: Six broad diagnostic groups could be identified in adults with pancytopenia. Megaloblastic anemia (D1) was the largest group comprising 57.5% of all patients. 11.7% of patients with pancytopenia were diagnosed as Aplastic anemia (D2).11.7% of patients with pancytopenia were diagnosed as leukemia/lymphoma (D3) such as lymphoma (1), metastatic anaplastic carcinoma (1), acute leukemia (11), and metastatic gastric carcinoma (1). 15% of patients with pancytopenia were diagnosed with infections (D4) such as complicated malaria cases (7), HIV (5), disseminated tuberculosis (4), viral (2). We also encountered (D5) 0.8% was Myelophthisis/Storage disorder as myelodysplastic syndrome (1) and 3.3% were other (D6) as reactive marrow (4). Conclusion: Pancytopenia is not a disease itself. It is a hematological feature of varying etiology with slight male preponderance. Megaloblastic anemia along with mixed nutritional anemia is leading cause of pancytopenia in India followed by infections being second and aplastic anemia and acute leukemia being third common causes. Keyword: Pancytopenia, Megaloblastic anemia, Nutritional anemia.


2014 ◽  
Author(s):  
Valerie Babinsky ◽  
Fadil Hannan ◽  
M Andrew Nesbit ◽  
Sarah Howles ◽  
Jianxin Hu ◽  
...  

2017 ◽  
Author(s):  
James Blackburn ◽  
Dinesh Giri ◽  
Senthil Seniappan ◽  
Mohammed Didi ◽  
Barbara Ciolka ◽  
...  

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