3 research outputs found
Coexistence of Plasma Cell Dyscrasia with Prefibrotic Stage of Primary Myelofibrosis: A Case Report
Introduction. Coexistence of myeloproliferative neoplasms with lymphoproliferative syndromes has been described in the past, whereas plasma cell dyscrasias seem to be the most common cases. Case Presentation. We present a case of a 59-year-old Caucasian female of Greek origin who presented with thrombocytosis. Clinical and laboratory investigation disclosed the presence of a smoldering myeloma with coexisting histological and molecular characteristics of primary myelofibrosis. The patient had the acquired point mutation V617F in the JAK2 gene but not the bcr-abl rearrangement and was treated for myelofibrosis with subsequent improvement of all haematological parameters without evidence of myelomatic evolution. Conclusion. We present the first case in the literature of a smoldering myeloma coexisting with primary myelofibrosis. The underlying pathogenetic mechanism could be either related to the presence of a pluripotent neoplastic stem cell capable to differentiate into both lymphoid and myeloid cells or be related to two separate nosologic entities
Micro-RNA analysis of renal biopsies in human lupus nephritis demonstrates up-regulated miR-422a driving reduction of kallikrein-related peptidase 4
Aberrancies in gene expression in immune effector cells and in
end-organs are implicated in lupus pathogenesis. To gain insights into
the mechanisms of tissue injury, we profiled the expression of
micro-RNAs in inflammatory kidney lesions of human lupus nephritis (LN).
Kidney specimens were from patients with active proliferative,
membranous or mixed LN and unaffected control tissue. Micro-RNAs were
quantified by TaqMan Low Density Arrays. Bioinformatics was employed to
predict gene targets, gene networks and perturbed signaling pathways.
Results were validated by transfection studies (luciferase assay,
real-time PCR) and in murine LN. Protein expression was determined by
immunoblotting and immunohistochemistry.
Twenty-four micro-RNAs were dysregulated (9 up-regulated, 15
down-regulated) in human LN compared with control renal tissue. Their
predicted gene targets participated in pathways associated with
TGF-beta, kinases, NF-kappa B, HNF4A, Wnt/beta-catenin, STAT3 and IL-4.
miR-422a showed the highest upregulation (17-fold) in active LN and
correlated with fibrinoid necrosis lesions (beta = 0.63, P = 0.002). In
transfection studies, miR-422a was found to directly target
kallikrein-related peptidase 4 (KLK4) mRNA. Concordantly, KLK4 mRNA was
significantly reduced in the kidneys of human and murine LN and
correlated inversely with miR-422a levels. Immunohistochemistry
confirmed reduced KLK4 protein expression in renal mesangial and tubular
epithelial cells in human and murine LN.
KLK4, a serine esterase with putative renoprotective properties, is
down-regulated by miR-422a in LN kidney suggesting that, in addition to
immune activation, local factors may be implicated in the disease