Dasatinib treatment markedly increases the number of large granular lymphocytes (LGLs) in a proportion of Ph leukemia patients, which associates with a better prognosis. The lymphocytosis is predominantly observed in cytomegalovirus (CMV)-seropositive patients, yet detectable CMV reactivation exists only in a small fraction of patients. Thus, etiology of the lymphocytosis still remains unclear. Here, we identified NK cells as the dominant LGLs expanding in dasatinib-treated patients, and applied principal component analysis (PCA) to an extensive panel of NK cell markers to explore underlying factors in NK cell activation. PCA displayed phenotypic divergence of NK cells that reflects CMV-associated differentiation and genetic differences, and the divergence was markedly augmented in CMV-seropositive dasatinib-treated patients. Notably, the CMV-associated highly differentiated status of NK cells was already observed at leukemia diagnosis, and was further enhanced after starting dasatinib in virtually all CMV-seropositive patients. Thus, the extensive characterization of NK cells by PCA strongly suggests that CMV is an essential factor in the NK cell activation, which progresses stepwise during leukemia and subsequent dasatinib treatment most likely by subclinical CMV reactivation. This study provides a rationale for the exploitation of CMV-associated NK cell activation for treatment of leukemias.
Human adenovirus (HAdV) is an important cause of the common cold and epidemic keratoconjunctivitis in immunocompetent individuals. In immunocompromised patients, HAdV can sometimes cause severe infection such as cystitis, gastroenteritis, pneumonia, encephalitis, hepatitis, or disseminated disease, resulting in significant morbidity and also mortality. In particular, severe cases have been reported in patients after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Indeed HAdV has been recognized as a pathogen that requires careful monitoring in allo‐HSCT patients. While HAdV hepatitis leading to severe acute liver failure is rare, such liver failure progresses rapidly and is often fatal. Unfortunately, HAdV hepatitis has few characteristic symptoms and physical findings, which makes it difficult to promptly confirm and start treatment. We report here four cases of HAdV hepatitis after allo‐HSCT and their autopsy findings.
We measured adenosine deaminase (ADA), lysozyme, fibronectin and carcinoembryonic antigen (CEA) in the pleural fluid of tuberculous and carcinomatous pleural effusion in order to discriminate these two groups. Tuberculous pleural effusion had significantly higher levels of ADAand lysozyme than did carcinomatous effusion. WhenADAactivity of more than 33 IU/7 is considered, diagnostic tests of tuberculous effusions showed a sensitivity of 100%, specificity of 95%and accuracy of 96%. A pleural fluid/serum ADAratio (pl-ADA/s-ADA) above 1.1 was found in 100% of tuberculous and in 53% of carcinomatous effusions (sensitivity 100%, specificity 47% , diagnostic accuracy 70%). A lysozyme level above 12^g/ml, selected as the discriminating limit, was found in 100% of tuberculous and in 17% of carcinomatous effusions (sensitivity 100% , specificity 83% , diagnostic accuracy 88%). Pleural fluid/serum lysozyme ratio (PL/SL) was also valuable in the discrimination of these two groups. Whenthe cutoff level of 1.2 was considered, diagnostic tests of tuberculous effusions showed a sensitivity of 100%, specificity of 88%and accuracy of 93%, respectively. The mean fibronectin concentration in pleural fluid with tuberculous effusion was significantly higher than that in carcinomatous effusion, but there was a marked overlap between these two groups. On the other hand, CEAwas significantly higher in carcinomatous effusions than in tuberculous effusions. At a cutoff level of 5 ng/ml, 53%of patients with carcinomatous effusion showed elevated pleural fluid CEAlevels, while none of the tuberculous effusion did (sensitivity 53% , specificity 100% , diagnostic accuracy 65%). The combined assay of ADA,lysozyme, pl-ADA/s-ADA, PL/SL and CEAprovide valuable information in the differentia] diagnosis between tuberculous and carcinomatous effusion, while fibronectin concentration can not be considered to have a definite diagnostic value.
Myeloproliferative neoplasms (MPNs), characterized by disorders of the hematopoietic stem cell, arises from kinase 2 (JAK2) V617F, calreticulin (CALR), myeloproliferative leukemia (MPL) mutations and a smaller number of other 'triple negative' forms where the driver mutation is not identified [1]. Mutations in these genes are almost entirely mutually exclusive. The accumulation of point mutations is also rare. Initiation and progression of these diseases by cytokine production are explained in 'A Human Inflammation Model of Cancer Development' [2]. JAK2V617F leads to the activation of genes involved in inflammatory signaling pathways including the activation of transforming growth factor β (TGF-β) [3-5]. We report the dipeptidyl-peptidase 4 (DPP4)-inhibitor rapidly increased and maintained the platelet count (PLC) in a patient with primary myelofibrosis (PMF) resulting from JAK2V617F abnormality.A 68-year-old man (BMI 19.4 kg/m2) diagnosed at 62 years with type 2 diabetes mellitus (T2DM) with accompanying overt nephropathy, receiving glimepiride therapy, was admitted to our hospital complaining of fatigue. Laboratory tests revealed pancytopenia (white blood cell (WBC) 2,200/μl, red blood cell (RBC) 1.25x10 6 /μl, hemoglobin 4.3 g/dL and platelet (PLT) 60x10 9 /L). Laboratory test results from 6 months prior to admission were normal except for blood glucose level (WBC 4,000/μl, RBC 3.52x10 6 /μl, hemoglobin 12.3 g/dL, PLT 161 x10 9 /L, postprandial blood glucose 362 mg/dL and hemoglobin A1c 7.9%). Chest radiographs, fecal occult blood tests andThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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