Triple-Negative Primary Myelofibrosis: A Bone Marrow Pathology Group Study.

Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm driven by canonical gene mutations in JAK2, CALR, or MPL in >80% of the cases. PMF that lacks these canonical alterations is termed triple-negative PMF (TN-PMF). The pathologic and genetic characteristics of TN-PMF compared with those of conventional PMF with canonical driver mutations (DM-PMF) have not been well studied.

Myeloid transformation of plasma cell myeloma: molecular evidence of clonal evolution revealed by next generation sequencing.

Background: Plasma cell myeloma (PCM) is a neoplasm of terminally differentiated B lymphocytes with molecular heterogeneity. Although therapy-related myeloid neoplasms are common in plasma cell myeloma patients after chemotherapy, transdifferentiation of plasma cell myeloma into myeloid neoplasms has not been reported in literature. Here we report a very rare case of myeloid neoplasm transformed from plasma cell myeloma.

Functional assessment of Toll-like receptor 2 and its relevance in patients with Staphylococcus aureus infection of joint prosthesis.

Staphylococcus aureus induces inflammation in experimental models through Toll-like receptor 2 (TLR2). The clinical relevance of this observation is debated. We evaluated the relationship between TLR2 R753Q single nucleotide polymorphism (SNP) and S aureus infection of joint prosthesis.

R753Q single-nucleotide polymorphism impairs toll-like receptor 2 recognition of hepatitis C virus core and nonstructural 3 proteins.

Background: Hepatitis C virus (HCV) core and nonstructural (NS) 3 proteins induce inflammation and immunity through a toll-like receptor (TLR) 2-dependent pathway. Individuals with the R753Q single-nucleotide polymorphism (SNP) in the TLR2 gene have increased the risk of allograft failure after liver transplantation for chronic hepatitis C.

Methods: To test the hypothesis that R753Q SNP impairs TLR2 recognition of HCV proteins, a series of in vitro experiments were performed wherein stable clones of wild-type TLR2-deficient human embryonic kidney (HEK) 293 cells and HEK293 cells transfected with wild-type (HEK293-TLR2) or variant TLR2 genes (HEK293-TLR2-R753Q) were stimulated with HCV core and NS3 proteins.

The R753Q polymorphism abrogates toll-like receptor 2 signaling in response to human cytomegalovirus.

Toll-like receptor 2 (TLR2) serves as a pattern recognition receptor that signals the presence of cytomegalovirus. Herein, we report that R753Q polymorphism paralyzes TLR2-mediated immune signaling in cells exposed to cytomegalovirus glycoprotein B. This immunologic impairment could serve as a biologic mechanism underlying the association between the TLR2 R753Q polymorphism and cytomegalovirus disease in humans.