Mutations in the nucleophosmin 1 (NPM1) gene are considered a founder event in the pathogenesis of acute myeloid leukemia (AML). To address the role of clonal evolution in relapsed NPM1-mutated ...(NPM1mut) AML, we applied high-resolution, genome-wide, single-nucleotide polymorphism array profiling to detect copy number alterations (CNAs) and uniparental disomies (UPDs) and performed comprehensive gene mutation screening in 53 paired bone marrow/peripheral blood samples obtained at diagnosis and relapse. At diagnosis, 15 aberrations (CNAs, n = 10; UPDs, n = 5) were identified in 13 patients (25%), whereas at relapse, 56 genomic alterations (CNAs, n = 46; UPDs, n = 10) were detected in 29 patients (55%) indicating an increase in genomic complexity. Recurrent aberrations acquired at relapse included deletions affecting tumor suppressor genes (ETV6 n = 3, TP53 n = 2, NF1 n = 2, WT1 n = 3, FHIT n = 2) and homozygous FLT3 mutations acquired via UPD13q (n = 7). DNMT3A mutations (DNMT3Amut) showed the highest stability (97%). Persistence of DNMT3Amut in 5 patients who lost NPM1mut at relapse suggests that DNMT3Amut may precede NPM1mut in AML pathogenesis. Of note, all relapse samples shared at least 1 genetic aberration with the matched primary AML sample, implying common ancestral clones. In conclusion, our study reveals novel insights into clonal evolution in NPM1mut AML.
• Relapsed AML with NPM1 mutation is genetically related to the primary leukemia and characterized by an increase in high-risk aberrations.• DNMT3A mutations show the highest stability and thus may precede NPM1 mutations.
Human alveolar echinococcosis (AE), which is caused by the cestode
(
)
, is an epidemiologically relevant issue in modern medicine and still poses a diagnostic and therapeutic challenge. Since ...diagnosis mainly relies on imaging procedures and serological testing, we retrospectively and comparatively analyzed the performance of an
IgG screening ELISA, whole serum IgE, and two specific confirmatory ELISA platforms using the defined
antigens Em2-Em18 (Em2+) and recombinant Em18 (recEm18). With special emphasis on the clinical usefulness of recEm18, we correlated the laboratory results with clinical characteristics and imaging findings in a large and well-characterized cohort of N = 124 AE patients, who were followed over several years after either surgical plus subsequent pharmacological treatment or pharmacotherapy alone. All patients had routinely received PET-CTI every two years. Our data reveal strong correlations for both
IgG and recEm18 with tracer uptake in PET-CTI and parasitic lesion size and number, suggesting additional clinical usefulness of recEm18 for certain constellations only, while IgG and Em2+ still appear reasonable and sensitive screening methods for initial diagnosis of AE. With this study, we aim to contribute to further optimizing medical care of AE patients. For instance, it might be reasonable to consider the replacement of some PET-CTI follow-ups by imaging procedures with less radiation exposure or serological means alone. Further studies that clarify the correlation of serological markers with ultrasound criteria might be particularly useful, and further retrospective as well as prospective investigations are justified in this context.
The main endemic areas of alveolar echinococcosis (AE) are in Central Europe and Western China. Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease ...can lead to further complications and may increase morbidity in patients with AE.
To evaluate vascular/biliary involvement in hepatic AE and its distant extrahepatic disease manifestations in an international collective was the aim.
Consecutively, five experienced examiners evaluated contrast-enhanced abdominal computed tomography (CT) scans for 200 patients with hepatic AE of each of four locations (
50) in Germany, France and China. Therefore, we retrospectively included the 50 most recent abdominal contrast-enhanced CT examinations at each center, performed because of hepatic AE from September 21, 2007 to March 21, 2018. AE liver lesions were classified according to the echinococcosis multilocularis Ulm classification for CT (EMUC-CT). Distant extrahepatic manifestations were documented either by whole body positron emission tomography-CT or with the addition of thoracic CT and cranial magnetic resonance imaging. Vascular/biliary involvement of the hepatic disease as well as the presence of distant extrahepatic manifestations were correlated with the EMUC-CT types of liver lesion. Statistical analysis was performed using SAS Version 9.4 (SAS Institute Inc., Cary, NC, United States).
Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe (
0.0091). A significant relationship was found between the presence of distant extrahepatic disease and AE liver lesion size (
0.0075). Vascular/biliary structures were involved by the liver lesions significantly more frequently in China than in Europe (
0.0001), and vascular/biliary involvement depended on lesion size. Different morphological types of AE liver lesions led to varying frequencies of vascular/biliary involvement and were associated with different frequencies of distant extrahepatic manifestations: Vascular/biliary involvement as a function of lesions primary morphology ranged from 5.88% of type IV liver lesions to 100% among type III lesions. Type IV differed significantly in these associations from types I, II, and III (
0.0001). With respect to extrahepatic disease, the primary morphology types IV and V of liver lesions were not associated with any case of distant extrahepatic disease. In contrast, distant extrahepatic manifestations in types I-III were found to varying degrees, with a maximum of 22% for type III.
Different CT morphological patterns of hepatic AE lesions influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations. There are intercontinental differences regarding the characteristics of AE manifestation.
PDF
