ABSTRACT
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the proliferation of one or more myeloid lineages. The current study demonstrates that three driver mutations were detected in 82.6% of 407 MPNs with a mutation distribution of JAK2 in 275 (67.6%), CALR in 55 (13.5%) and MPL in 6 (1.5%). The mutations were mutually exclusive in principle except in one patient with both CALR and MPL mutations. The driver mutation directed the pathologic features of MPNs, including lineage hyperplasia, laboratory findings and clinical presentation. JAK2-mutated MPN showed erythroid, granulocytic and/or megakaryocytic hyperplasia whereas CALR- and MPL-mutated MPNs displayed granulocytic and/or megakaryocytic hyperplasia. The lineage hyperplasia was closely associated with a higher mutant allele burden and peripheral cytosis. These findings corroborated that the lineage hyperplasia consisted of clonal proliferation of each hematopoietic lineage acquiring driver mutations. Our study has also demonstrated that bone marrow (BM) fibrosis was associated with disease progression. Patients with overt fibrosis (grade ⩾2) presented an increased mutant allele burden (P<0.001), an increase in chromosomal abnormalities (P<0.001) and a poor prognosis (P<0.001). Moreover, among patients with overt fibrosis, all patients with wild-type JAK2/CALR/MPL (triple-negative) showed genomic alterations by genome-wide microarray study and revealed the poorest overall survival, followed by JAK2-mutated MPNs. The genetic–pathologic characteristics provided the information for understanding disease pathogenesis and the progression of MPNs. The prognostic significance of the driver mutation and BM fibrosis suggests the necessity of a prospective therapeutic strategy to improve the clinical outcome.
Subject(s)
Humans , Alleles , Bone Marrow , Chromosome Aberrations , Disease Progression , Fibrosis , Hematopoietic Stem Cells , Hyperplasia , Prognosis , Prospective StudiesABSTRACT
BACKGROUND: Three chromogenic media using direct inoculation were compared with enriched enterococcosel broth for vancomycin-resistant Enterococcus faecium and/or Enterococcus faecalis (VRE) surveillance. METHODS: A total of 174 rectal swabs were included for VRE surveillance. The specimens were transferred in enterococcosel broth (EB). An aliquot of the broth was inoculated onto Brilliance VRE, chromID VRE, and VRESelect media and incubated for up to 48 h. We examined each media and EB after 24 h and 48 h of incubation. When appropriately colored colonies were observed, identification was confirmed using the VITEK-2 system and/or VITEK MS. Vancomycin susceptibility was confirmed by disk diffusion test. The presence of resistance genes was confirmed using Anyplex VanR Real-time Detection (Seegene, Korea). RESULTS: Of the 174 rectal swab specimens, 73 VRE were isolated. For enterococcosel broth, Brilliance VRE, chromID VRE, and VRESelect, the sensitivity at 24 h was 79.2%, 83.3%, 79.2%, and 79.2%, respectively. The sensitivity at 48 h was 91.7%, 93.1%, 91.4%, and 90.3%, respectively. The specificity at 24 h was 85.3%, 97.1%, 98.0%, and 98.0%, while that at 48 h was 79.4%, 85.3%, 95.2%, and 95.1%, respectively. The specificity of chromogenic media at 24 h and 48 h was significantly higher than that of EB. Furthermore, the specificity at 48 h was significantly higher for chromID VRE and VRESelect than Brilliance VRE, although color distinction was easier with VRESelect. CONCLUSION: Based on our results, use of chromID VRE or VRESelect is more reliable and convenient for screening of VRE. In addition, five vanA-positive Enterococcus gallinarum, Enterococcus avium and Enterococcus durans were isolated, and two of them (one E. avium and one E. durans) were detected only on VRESelect.
Subject(s)
Diffusion , Enterococcus , Enterococcus faecalis , Enterococcus faecium , Mass Screening , Sensitivity and Specificity , VancomycinABSTRACT
No abstract available.