scholarly journals Apoptotic Ablation of Platelets Reduces Atherosclerosis in Mice With Diabetes

2021 ◽  
Vol 41 (3) ◽  
pp. 1167-1178
Author(s):  
Man K.S. Lee ◽  
Michael J. Kraakman ◽  
Dragana Dragoljevic ◽  
Nordin M.J. Hanssen ◽  
Michelle C. Flynn ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Bone Marrow ◽  
B Cell ◽  
Disease Risk ◽  
Cell Lymphoma ◽  
Cardiovascular Disease Risk ◽  
Atherosclerotic Lesion ◽  
B Cell Lymphoma ◽  
Loss Of Function ◽  
Wild Type Littermate

Objective: People with diabetes are at a significantly higher risk of cardiovascular disease, in part, due to accelerated atherosclerosis. Diabetic subjects have increased number of platelets that are activated, more reactive, and respond suboptimally to antiplatelet therapies. We hypothesized that reducing platelet numbers by inducing their premature apoptotic death would decrease atherosclerosis. Approach and Results: This was achieved by targeting the antiapoptotic protein Bcl-x L (B-cell lymphoma-extra large; which is essential for platelet viability) via distinct genetic and pharmacological approaches. In the former, we transplanted bone marrow from mice carrying the Tyr15 to Cys loss of function allele of Bcl-x (known as Bcl-x Plt20 ) or wild-type littermate controls into atherosclerotic-prone Ldlr +/− mice made diabetic with streptozotocin and fed a Western diet. Reduced Bcl-x L function in hematopoietic cells significantly decreased platelet numbers, exclusive of other hematologic changes. This led to a significant reduction in atherosclerotic lesion formation in Bcl-x Plt20 bone marrow transplanted Ldlr +/− mice. To assess the potential therapeutic relevance of reducing platelets in atherosclerosis, we next targeted Bcl-x L with a pharmacological strategy. This was achieved by low-dose administration of the BH3 (B-cell lymphoma-2 homology domain 3) mimetic, ABT-737 triweekly, in diabetic Apoe −/− mice for the final 6 weeks of a 12-week study. ABT-737 normalized platelet numbers along with platelet and leukocyte activation to that of nondiabetic controls, significantly reducing atherosclerosis while promoting a more stable plaque phenotype. Conclusions: These studies suggest that selectively reducing circulating platelets, by targeting Bcl-x L to promote platelet apoptosis, can reduce atherosclerosis and lower cardiovascular disease risk in diabetes. Graphic Abstract: A graphic abstract is available for this article.

A Challenging Case of A Myeloid Sarcoma Misdiagnosed as High Grade B-Cell Lymphoma

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S97-S97
Author(s):  
A Herrmann ◽  
B Mai ◽  
S Elzamly ◽  
A Wahed ◽  
A Nguyen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Myeloid Sarcoma ◽  
Proliferation Index ◽  
High Grade ◽  
Cell Markers ◽  
Thoracolumbar Region ◽  
The Right

Abstract Introduction/Objective A 46-year-old female presented with severe back pain associated with progressive bilateral lower extremity weakness and paresthesia, urinary retention, and constipation. Computed tomography revealed a retroperitoneal mass encasing the right psoas muscle, obstructing the right kidney, and extending to the thoracolumbar region resulting in severe spinal compression. An epidural tumor resection was subsequently performed at an outside hospital. Methods Histological sections showed sheets of blastoid neoplastic cells with intermediate to large nuclei, irregular membranes, fine chromatin, and prominent nucleoli. Immunohistochemical stains showed that these cells were positive for CD43, CD79a (weak, focal), BCL2, C-MYC, and PAX5 (weak, focal) and negative for CD10, CD20, CD30, ALK1, BCL6, MUM1, and Tdt. The Ki-67 proliferation index was 75-80%. With this immunophenotype, this patient was diagnosed with a high grade B-cell lymphoma and transferred to our institution for further work-up. On review of the slides, further immunohistochemical testing was requested which revealed positivity for CD117 and myeloperoxidase (MPO). Results The overall morphological and immunophenotypical features are most compatible with myeloid sarcoma (MS) with aberrant expression of B-cell markers and this patient’s diagnosis was amended. Interestingly, the patient’s bone marrow examination only showed 2% myeloblasts with left shifted granulocytosis and concurrent fluorescence in situ hybridization (FISH) studies were negative. Conclusion A literature review showed that 40-50% of MS are misdiagnosed as lymphoma. MS can frequently stain with B-cell or T-cell markers, as seen in this case, which makes it challenging for an accurate diagnosis and sub- classification. In addition, our case is interesting in that there was only extramedullary presentation without bone marrow involvement. Typically, MS develops after the diagnosis of acute myeloid leukemia (AML) with an incidence of 3–5% after AML. It can also manifest de novo in healthy patients, who then go on to develop AML months to years later. Therefore, this patient will require close follow-up.

scholarly journals Tumor staging in a Beagle dog with concomitant large B-cell lymphoma and T-cell acute lymphoblastic leukemia

2021 ◽  
pp. 104063872110110
Author(s):  
Alessandro Ferrari ◽  
Marzia Cozzi ◽  
Luca Aresu ◽  
Valeria Martini
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Tumor Staging ◽  
Lymphoblastic Leukemia ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Cell Acute Lymphoblastic Leukemia

An 8-y-old spayed female Beagle dog was presented with peripheral lymphadenomegaly. Lymph node cytology and flow cytometry led to the diagnosis of large B-cell lymphoma (LBCL). We detected minimal percentages of LBCL cells in peripheral blood and bone marrow samples. However, a monomorphic population of neoplastic cells different from those found in the lymph node was found in the bone marrow. T-cell acute lymphoblastic leukemia was suspected based on flow cytometric immunophenotyping. PCR for antigen receptor rearrangement (PARR) revealed clonal rearrangement of both B-cell and T-cell receptors, and the presence of both neoplastic clones in the lymph node, peripheral blood, and bone marrow. The dog was treated with multi-agent chemotherapy but died 46 d following diagnosis. Tumor staging and patient classification are needed to accurately establish a prognosis and select the most appropriate therapeutic protocol.

scholarly journals Bone Marrow Molecular Markers Associated with Relapsed/Refractory Activated B-Cell-Like Diffuse Large B-Cell Lymphoma

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Di Wang ◽  
Peng Liu ◽  
Yue Zhang ◽  
Hui-Ying Liu ◽  
Di Shen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Molecular Markers ◽  
B Cell ◽  
Bone Marrow Aspirate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Significant Finding ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is a common subtype of non-Hodgkin’s lymphoma and is very likely to infiltrate the bone marrow. Over 30% of patients are converted to relapsed/refractory DLBCL after first-line rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, with a poor prognosis. Our aim was to identify molecular markers that might be utilized to predict relapsed/refractory ABC-DLBCL patients. Hence, we collected bone marrow aspirate smears from 202 patients with ABC-DLBCL and detected expression of bone marrow molecular marker proteins by immunocytochemistry. Signal transducer and activator of transcription (Stat)3, nuclear factor (NF)-κB p65, Syk, Bruton’s tyrosine kinase (BTK), and Bcl2 proteins were strongly expressed in bone marrow aspirate smears of ABC-DLBCL patients. The same smear could present positive expression of multiple proteins simultaneously. Positive combinations of protein expression were associated with resistance. The most significant finding was that the Stat3+NF-κB+ group developed resistance, which was significantly higher than that of the Stat3-NF-κB-group (80 vs. 14%). There was a significant difference in two-year relapse-free survival between protein-positive and protein-negative combinations of Stat3-NF-κB (P = 0.005), Bcl2-Stat3 (P = 0.009), Bcl2-Pax5 (P = 0.003), and BTK-Syk (P < 0.001). Thus, we detected key molecules in multiple signaling pathways in bone marrow aspirate smears. At the same time, the results provide further clinical evidence of ABC-DLBCL drug-resistant molecules and provide a theoretical basis for rational second-line treatment after drug resistance.

scholarly journals Primary Bone Marrow B-Cell Lymphoma Undetected by Multiple Imaging Modalities That Initially Presented with Hypercalcemia

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Jin Sae Yoo ◽  
Juwon Kim ◽  
Hyeong Ju Kwon ◽  
Jung Soo Lim
Keyword(s):  
Computed Tomography ◽  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
Hematologic Malignancy ◽  
B Cell Lymphoma ◽  
Severe Hypercalcemia ◽  
Multiple Imaging ◽  
Primary Bone ◽  
Primary Bone Marrow

Purpose. We report a rare case of severe hypercalcemia that was ultimately diagnosed as primary bone marrow diffuse large B-cell lymphoma (BCL). Case Report. A 74-year-old male patient visited our hospital complaining of tenderness and swelling of the left knee caused by supracondylar fracture of the left distal femur. His initial blood tests showed a serum calcium level of 13.9 mg/dL, inorganic phosphorus of 4.34 mg/dL, and a serum creatinine level of 1.54 mg/dL. A serum assay of intact parathyroid hormone showed 5.24 pg/mL, and the patient’s serum 25(OH)D level was 22.33 ng/mL. To exclude malignancy, we performed imaging studies, including abdomen or chest computed tomography and positron emission tomography-computed tomography; however, no suspicious lesion was found, although the serum PTH-related peptide level was elevated at 4.0 pmol/L. A bone marrow biopsy was performed to identify any hidden hematologic malignancy. As a result, the pathology of bone marrow confirmed the presence of atypical lymphocytes that stained positive for the CD20 marker, which is consistent with BCL involving the bone marrow. Conclusion. This case highlights the importance of pursuing a thorough workup for rare underlying causes of hypercalcemia when parathyroid-related etiologies can be excluded.

scholarly journals Circulating Proangiogenic Cell Activity Is Associated with Cardiovascular Disease Risk

2012 ◽  
Vol 17 (9) ◽  
pp. 1163-1170 ◽  
Author(s):  
Kreton Mavromatis ◽  
Konstantinos Aznaouridis ◽  
Ibhar Al Mheid ◽  
Emir Veledar ◽  
Saurabh Dhawan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Bone Marrow ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Cell Activity ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cvd Risk ◽  
The Relationship

Vascular injury mobilizes bone marrow–derived proangiogenic cells into the circulation, where these cells can facilitate vascular repair and new vessel formation. We sought to determine the relationship between a new biomarker of circulating bone marrow–derived proangiogenic cell activity, the presence of atherosclerotic cardiovascular disease (CVD) and its risk factors, and clinical outcomes. Circulating proangiogenic cell activity was estimated using a reproducible angiogenic colony-forming unit (CFU-A) assay in 532 clinically stable subjects aged 20 to 90 years and ranging in the CVD risk spectrum from those who are healthy without risk factors to those with active CVD. CFU-A counts increased with the burden of CVD risk factors ( p < 0.001). CFU-A counts were higher in subjects with symptomatic CVD than in those without ( p < 0.001). During follow-up of 232 subjects with CVD, CFU-A counts were higher in those with death, myocardial infarction, or stroke than in those without (110 [70–173] vs 84 [51–136], p = 0.01). Therefore, we conclude that circulating proangiogenic cell activity, as estimated by CFU-A counts, increases with CVD risk factor burden and in the presence of established CVD. Furthermore, higher circulating proangiogenic cell activity is associated with worse clinical outcome in those with CVD.

Follicular large-cell lymphoma treated with intensive chemotherapy: an analysis of 89 cases included in the LNH87 trial and comparison with the outcome of diffuse large B-cell lymphoma. Groupe d'Etude des Lymphomes de l'Adulte.

1997 ◽  
Vol 15 (4) ◽  
pp. 1654-1663 ◽  
Author(s):  
D Wendum ◽  
C Sebban ◽  
P Gaulard ◽  
B Coiffier ◽  
H Tilly ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Prognostic Factors ◽  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Intensive Chemotherapy ◽  
Large B Cell Lymphoma ◽  
Beta 2 Microglobulin

PURPOSE The aims of this study were as follows: (1) to analyze clinical, histopathologic characteristics, treatment outcome, and prognostic factors of patients with follicular large-cell lymphoma (FLCL); and (2) to compare them with those of patients with diffuse large B-cell lymphoma (DLCL) treated in the same therapeutic trial. PATIENTS AND METHODS Eighty-nine FLCL patients who were histologically reviewed and who received an intensive chemotherapy regimen according to the LNH 87 protocol were analyzed and compared with 1,096 B-cell DLCL patients included in the same protocol. RESULTS After intensive induction treatment, 59 patients (67%) achieved a complete remission [CR]. Estimated 5-year survival was 59%, and estimated 5-year freedom from progression (FFP) was 39%. Prognostic factors associated with shorter FFP were age greater than 60 years (P = .02), advanced clinical stage (P = .01), abnormal lactic dehydrogenase (LDH) level (P = .02), abnormal beta-2 microglobulin (P = .02), B symptoms (P = .03), bone marrow involvement (P = .04), and high expression of bcl-2 protein (P = .05). When compared with B-cell DLCL patients, FLCL patients were younger (P = .02), had a better Eastern Cooperative Oncology Group (ECOG) status (P = .05), less bulky mass (P = .04), more advanced clinical stages (P < .001), and more bone marrow involvement (P = .02). No significant difference was observed between FLCL and DLCL patients for response to therapy (67% v 67% of CR), 5-year overall survival (58% v 51%), 5-year disease-free survival (53% v 57%), or FFP survival (39% v 43%). CONCLUSION FLCL patients have a favorable response rate and survival when treated with intensive chemotherapy. Their outcome is similar to that of B-cell DLCL patients, and a long-term FFP is observed for a substantial number of patients. Some adverse prognostic factors (including those of the International Prognostic Index, bone marrow involvement, and beta-2 microglobulin) have been identified to define a subset of patients who require other therapeutic approach.

Hemophagocytic Syndrome in a Case of Splenic Large B-Cell Lymphoma

1996 ◽  
Vol 82 (6) ◽  
pp. 621-624 ◽  
Author(s):  
Gualtiero Büchi ◽  
Giuseppe Termine ◽  
Renzo Orlassino ◽  
Mauro Pagliarino ◽  
Roberto Boero ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Nodes ◽  
B Cell ◽  
Diagnostic Criteria ◽  
Hemophagocytic Syndrome ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Peripheral Lymph ◽  
Large B Cell

A case of splenic large B-cell lymphoma with hemophagocytic syndrome is reported. The difficulties of diagnosis are emphasized especially when peripheral lymph nodes or bone marrow lymphomatous infiltration are not present. Diagnostic criteria for hemophagocytic syndrome and their relationship with the pathogenesis of the disease are also stressed.

Auer rod-like inclusions in the cytoplasm of B-cell lymphoma cells with bone marrow infiltration

2019 ◽  
Vol 77 ◽  
pp. 6-11
Author(s):  
Zhanxi Gao ◽  
Fang Cui ◽  
Mei Liu ◽  
Yukai Guo ◽  
Yuhong Hu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Bone Marrow Infiltration ◽  
Lymphoma Cells
Sign in / Sign up

Export Citation Format

Share Document