Publications by authors named "Bryan T Ciccarelli"
Expression of the p210 BCR/ABL1 fusion protein has been described in virtually all patients with chronic myelogenous leukemia (CML). Previous studies have identified a guanine nucleotide exchange factor (RhoGEF) domain within BCR that is retained in p210 BCR/ABL1. Missense mutations at residues T654 (T654K) and F547 (F547L) within this domain have been reported in a CML patient in blast crisis (BC).
View Article and Find Full Text PDFDBS/MCF2L has been recently identified as a risk locus for osteoarthritis. It encodes a guanine nucleotide exchange factor (Dbs) that has been shown to regulate both normal and tumor cell motility. In the current study, we have determined that endogenous Dbs is predominantly expressed as 2 isoforms, a 130 kDa form (Dbs-130) that is localized to the Golgi complex, and an 80 kDa form (Dbs-80) that is localized to the endoplasmic reticulum (ER).
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- Anemia is common in patients with Waldenström macroglobulinemia (WM) and isn’t always linked to bone marrow issues; hepcidin plays a role in iron absorption and can be elevated in these patients.
- A study on 108 untreated anemic WM patients found that over half had low transferrin saturation (TSAT) levels, with some showing significantly low levels.
- Patients with the lowest TSAT who received parenteral iron therapy demonstrated significant improvements in hematocrit, mean corpuscular volume, and TSAT, indicating that regular screening could help identify those needing this treatment.
Soluble CD27 (sCD27) is produced by Waldenström's macroglobulinemia (WM) cells, with high levels found in WM patients which may facilitate disease expansion. Matrix metalloproteinases (MMP) may facilitate sCD27 release by cleavage of CD27. By gene expression analysis, we observed significantly higher transcription levels of MMP-8 and MMP-9, with 58.
View Article and Find Full Text PDFWaldenström's macroglobulinemia (WM) patients often present with anemia as their primary disease manifestation that may be related to hepcidin, an important regulator of iron homeostasis. We therefore determined hepcidin levels in 53 WM patients, and 20 age-matched healthy patient donors by hepcidin-25 ELISA. Serum hepcidin levels were elevated in WM patients versus healthy patients (P=.
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- Hypogammaglobulinemia, particularly low levels of IgA and IgG, is frequently observed in patients with Waldenström's macroglobulinemia, where it may be related to tumor-induced suppression of antibody production.
- A study involving 207 untreated patients revealed that a significant percentage had low serum IgA (63.3%) and IgG (58.0%), but these low levels did not correlate with overall disease severity or recurrent infections.
- Despite treatments achieving remission, low IgA and IgG levels persisted, and a mutation in a gene related to immunoglobulin deficiency was noted in one patient, suggesting a need for further investigation into this genetic pathway.
Article Synopsis
- The study investigates the impact of rituximab treatment on patients with Waldenström's macroglobulinemia (WM), specifically focusing on the fluctuations of IgM levels and the role of soluble CD27 (sCD27) as a potential disease burden marker.
- Eight patients showed an IgM increase after rituximab treatment, where IgM levels rose significantly while sCD27 levels dropped, providing insight into the disease's clinical response.
- sCD27 remains stable during plasmapheresis and rituximab treatment, suggesting it could be a reliable marker for monitoring disease burden and predicting treatment outcomes in WM patients.
Purpose: Nucleoside analogs (NAs) are considered as appropriate agents in the treatment of Waldenström macroglobulinemia (WM), a lymphoplasmacytic lymphoma. Sporadic reports on increased incidence of transformation to high-grade non-Hodgkin's lymphoma and development of therapy-related myelodysplasia/acute leukemia (t-MDS/AML) among patients with WM treated with NAs prompted us to examine the incidence of such events in a large population of patients with WM.
Patients And Methods: We examined the incidence of these events in 439 patients with WM, 193 and 136 of whom were previously treated with and without an NA, respectively, and 110 of whom had similar long-term follow-up without treatment.
Thalidomide enhances rituximab-mediated, antibody-dependent, cell-mediated cytotoxicity. We therefore conducted a phase 2 study using thalidomide and rituximab in symptomatic Waldenstrom macroglobulinemia (WM) patients naive to either agent. Intended therapy consisted of daily thalidomide (200 mg for 2 weeks, then 400 mg for 50 weeks) and rituximab (375 mg/m(2) per week) dosed on weeks 2 to 5 and 13 to 16.
View Article and Find Full Text PDFWaldenström macroglobulinemia (WM) is a B-cell malignancy characterized by an IgM monoclonal gammopathy and bone marrow (BM) infiltration with lymphoplasmacytic cells (LPCs). Excess mast cells (MCs) are commonly present in WM, and provide growth and survival signals to LPCs through several TNF family ligands (CD40L, a proliferation-inducing ligand [APRIL], and B-lymphocyte stimulator factor [BLYS]). As part of these studies, we demonstrated that WM LPCs secrete soluble CD27 (sCD27), which is elevated in patients with WM (P < .
View Article and Find Full Text PDFThe presence of valine (V) at position 158 of FcgammaRllla (CD16) is known to improve clinical response to rituximab in indolent non-Hodgkin lymphoma (NHL). Little is known about the basic mechanisms for this observation. We examined natural killer (NK) cells from healthy donors representing the FcgammaRIIIa-158 polymorphic subgroups (V/V, V/F, and F/F) for gene transcript and cell surface CD16 expression, rituximab binding, and rituximab-dependent NK cell-mediated cytotoxicity.
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