Intravascular Large B-cell Lymphoma Diagnosed by Nasal Biopsy in a Patient Presenting with Bilateral Ptosis and Ophthalmoplegia.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of lymphoma, involving the lumen of predominantly small blood vessels, especially capillaries. The orbit is an uncommon site of involvement for IVLBCL, and diagnosis before autopsy is even more rare as most cases are established post-mortem. Herein, the authors describe a 73-year-old male who presented with 3 weeks of progressive bilateral ptosis and ophthalmoplegia.

NP-ALT, a Liposomal:Peptide Drug, Blocks p27Kip1 Phosphorylation to Induce Oxidative Stress, Necroptosis, and Regression in Therapy-Resistant Breast Cancer Cells.

Resistance to cyclin D-CDK4/6 inhibitors (CDK4/6i) represents an unmet clinical need and is frequently caused by compensatory CDK2 activity. Here we describe a novel strategy to prevent CDK4i resistance by using a therapeutic liposomal:peptide formulation, NP-ALT, to inhibit the tyrosine phosphorylation of p27Kip1(CDKN1B), which in turn inhibits both CDK4/6 and CDK2. We find that NP-ALT blocks proliferation in HR+ breast cancer cells, as well as CDK4i-resistant cell types, including triple negative breast cancer (TNBC).

Tyrosine Phosphorylation of p27Kip1 Correlates with Palbociclib Responsiveness in Breast Cancer Tumor Cells Grown in Explant Culture.

Cdk4-targeting drugs, such as palbociclib, are approved for metastatic ER/PR, Her2 breast cancer. However, other than loss of retinoblastoma, which is very rare in this subset, there are no biomarkers to predict response. Cyclin D or cdk4 levels are not by themselves indicative, because p27Kip1 is required for cyclin D-cdk4 complex activation.

Dual Inhibition of CDK4 and CDK2 via Targeting p27 Tyrosine Phosphorylation Induces a Potent and Durable Response in Breast Cancer Cells.

Cyclin-dependent kinase 4/6 (CDK4/6)-specific inhibitors, such as palbociclib, have shown clinical efficacy, but primary or secondary resistance has emerged as a problem. To develop more effective therapeutic approaches, investigation is needed into the mechanisms of resistance or adaption. Here, it is demonstrated that CDK2 compensates for loss of CDK4 activity to rescue palbociclib-arrested breast cancer cells, suggesting that inhibition of both kinases is required to achieve durable response.

Nodular Lymphocyte Predominant Hodgkin Lymphoma versus T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: A Diagnostic Challenge.

Lymphomas with overlapping histological features of two distinct entities cause difficulty in classification. Their classification is of particular significance when the two alternatives require different treatment modalities. We present a diagnostically challenging case of a nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) with features of T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL).

Loss of Foxp3 is associated with CD30 expression in the anaplastic large cell subtype of adult T-cell leukemia/lymphoma (ATLL) in US/Caribbean patients: potential therapeutic implications for CD30 antibody-mediated therapy.

Adult T-cell leukemia/lymphoma (ATLL) is caused by the HTLV-1 virus, endemic to Japan and the Caribbean, and is likely derived from cells with the T-regulatory phenotype. The malignant cells express IL2 receptor α (CD25), and the majority express transcription factor Forkhead box P3 (Foxp3), in addition to T-cell markers. Occasional cases express CD30.

Transcription factors TFE3 and TFEB are critical for CD40 ligand expression and thymus-dependent humoral immunity.

TFE3 and TFEB are broadly expressed transcription factors related to the transcription factor Mitf. Although they have been linked to cytokine signaling pathways in nonlymphoid cells, their function in T cells is unknown. TFE3-deficient mice are phenotypically normal, whereas TFEB deficiency causes early embryonic death.

T cell lymphoma associated with myelofibrosis.

Myelofibrosis is most frequently associated with certain primary myeloproliferative disorders,but is rare in lymphoid neoplasms. We report the fourth case associated with T-cell lymphoma, involving bone marrow, lymph nodes and spleen. Marked extramedullary hematopoiesis was present.