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Cancer Cytopathology Jun 2024
Use of ultrasensitive RNA in situ hybridization for kappa and lambda light chains assists in the differential diagnosis of B-cell non-Hodgkin and Hodgkin lymphomas in cytopathology practice.
PubMed: 38824408
DOI: 10.1002/cncy.22834 -
Lancet (London, England) Jun 2024
Topics: Humans; Male; Lymphomatoid Granulomatosis; Adult; Addison Disease
PubMed: 38823995
DOI: 10.1016/S0140-6736(24)00974-7 -
Cardiovascular Pathology : the Official... May 2024A 65-year-old man with previous history of smoking, controlled HIV infection, treated hepatitis B infection, and type III cryoglobulinemia, was admitted due to right...
A 65-year-old man with previous history of smoking, controlled HIV infection, treated hepatitis B infection, and type III cryoglobulinemia, was admitted due to right heart failure symptoms and significant weight loss. Despite being haemodynamically stable, he had periods of 1:1 conduction atrial flutter and presented with respiratory alkalosis and metabolic acidosis, as well as acute kidney and hepatic dysfunction, elevated D-dimer and cardiac markers. He underwent imaging with chest computed tomography and echocardiogram that confirmed pulmonary embolism and most notably revealed a significant sized cardiac mass causing almost complete obstruction of the right chambers, with no cleavage plane with the myocardial walls and tricuspid valve. Cardiac magnetic resonance was highly suggestive of malignancy. Cardiac surgery for mass excision and endomyocardial biopsy for diagnosis were considered, but the patient died with obstructive shock unresponsive to medical treatment. The autopsy revealed a primary unspecified diffuse large B-cell lymphoma.
PubMed: 38823525
DOI: 10.1016/j.carpath.2024.107664 -
Molecular Therapy : the Journal of the... May 2024In recent years, the therapeutic landscape for hematological malignancies has markedly advanced, particularly since the inaugural approval of autologous chimeric antigen... (Review)
Review
In recent years, the therapeutic landscape for hematological malignancies has markedly advanced, particularly since the inaugural approval of autologous chimeric antigen receptor T cell (CAR-T) therapy in 2017 for relapsed/refractory acute lymphoblastic leukemia (ALL). Autologous CAR-T therapy involves the genetic modification of a patient's T cells to specifically identify and attack cancer cells, while bispecific antibodies (BsAbs) function by binding to both cancer cells and immune cells simultaneously, thereby triggering an immune response against the tumor. The subsequent approval of various CAR-T therapies and BsAbs have revolutionized the treatment of multiple hematological malignancies, highlighting high response rates and a subset of patients achieving prolonged disease control. This review explores the mechanisms underlying autologous CAR-T therapies and BsAbs, focusing on their clinical application in multiple myeloma, ALL, and non-Hodgkin lymphoma. We provide comprehensive insights into their individual efficacy, limitations concerning broad application, and the potential of combination therapies. These upcoming strategies aim to propel the field forward, paving the way for safer and more effective therapeutic interventions in hematological malignancies.
PubMed: 38822527
DOI: 10.1016/j.ymthe.2024.05.039 -
Genome Biology May 2024Targeted therapies exploiting vulnerabilities of cancer cells hold promise for improving patient outcome and reducing side-effects of chemotherapy. However, efficacy of...
BACKGROUND
Targeted therapies exploiting vulnerabilities of cancer cells hold promise for improving patient outcome and reducing side-effects of chemotherapy. However, efficacy of precision therapies is limited in part because of tumor cell heterogeneity. A better mechanistic understanding of how drug effect is linked to cancer cell state diversity is crucial for identifying effective combination therapies that can prevent disease recurrence.
RESULTS
Here, we characterize the effect of G2/M checkpoint inhibition in acute lymphoblastic leukemia (ALL) and demonstrate that WEE1 targeted therapy impinges on cell fate decision regulatory circuits. We find the highest inhibition of recovery of proliferation in ALL cells with KMT2A-rearrangements. Single-cell RNA-seq and ATAC-seq of RS4;11 cells harboring KMT2A::AFF1, treated with the WEE1 inhibitor AZD1775, reveal diversification of cell states, with a fraction of cells exhibiting strong activation of p53-driven processes linked to apoptosis and senescence, and disruption of a core KMT2A-RUNX1-MYC regulatory network. In this cell state diversification induced by WEE1 inhibition, a subpopulation transitions to a drug tolerant cell state characterized by activation of transcription factors regulating pre-B cell fate, lipid metabolism, and pre-BCR signaling in a reversible manner. Sequential treatment with BCR-signaling inhibitors dasatinib, ibrutinib, or perturbing metabolism by fatostatin or AZD2014 effectively counteracts drug tolerance by inducing cell death and repressing stemness markers.
CONCLUSIONS
Collectively, our findings provide new insights into the tight connectivity of gene regulatory programs associated with cell cycle and cell fate regulation, and a rationale for sequential administration of WEE1 inhibitors with low toxicity inhibitors of pre-BCR signaling or metabolism.
Topics: Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Histone-Lysine N-Methyltransferase; Cell Cycle Proteins; Cell Line, Tumor; Pyrimidines; Pyrimidinones; Myeloid-Lymphoid Leukemia Protein; Pyrazoles; Protein-Tyrosine Kinases; Antineoplastic Agents; Cell Cycle; Core Binding Factor Alpha 2 Subunit
PubMed: 38822412
DOI: 10.1186/s13059-024-03260-4 -
Blood Cancer Journal May 2024Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma with sparse tumor B-cells and a favorable prognosis. Variant growth patterns of NLPHL,...
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma with sparse tumor B-cells and a favorable prognosis. Variant growth patterns of NLPHL, however, often show advanced stage, progression to T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) and a worse prognosis. We studied the tumor microenvironment (TME) of NLPHL and THRLBCL using highplex imaging and spatial profiling at the single cell level. Our findings show distinct differences in TME composition and spatial configuration that differ among typical and variant NLPHL and THRLBCL. Typical NLPHL show abundant helper T-cell subsets, while THRLBCL show abundant cytotoxic T-cells and macrophages. Tumor B-cell size and content is lowest in typical NLPHL, followed by variant NLPHL, and highest in THRLBCL, whereas an opposite trend characterized TME B-cells. CD4/CD8 double-positive T-cells are seen in all NLPHL but not in the majority of THRLBCL and are spatially distant from LP-cells and TFH-rosettes. The differences in macrophage/monocyte content in distinguishing NLPHL pattern E from THRLBCL is further corroborated in independent cohorts of cases. Our results validate the current approach to classification and in addition provide novel insights that could be leveraged to refine clinical management for patients with this spectrum of lymphomas.
Topics: Humans; Hodgkin Disease; Tumor Microenvironment; Lymphoma, Large B-Cell, Diffuse; Male; Histiocytes; Female; Middle Aged; Adult; T-Lymphocytes
PubMed: 38821935
DOI: 10.1038/s41408-024-01073-z -
Medicina Clinica May 2024
PubMed: 38821827
DOI: 10.1016/j.medcli.2024.01.034 -
Clinics in Laboratory Medicine Jun 2024Lymphoid malignancies are a broad and heterogeneous group of neoplasms. In the past decade, the genetic landscape of these tumors has been explored and cataloged in fine... (Review)
Review
Lymphoid malignancies are a broad and heterogeneous group of neoplasms. In the past decade, the genetic landscape of these tumors has been explored and cataloged in fine detail offering a glimpse into the mechanisms of lymphomagenesis and new opportunities to translate these findings into patient management. A myriad of studies have demonstrated both distinctive and overlapping molecular and chromosomal abnormalities that have influenced the diagnosis and classification of lymphoma, disease prognosis, and treatment selection.
Topics: Humans; Lymphoma; Pathology, Molecular; Chromosome Aberrations
PubMed: 38821649
DOI: 10.1016/j.cll.2023.08.014 -
BMJ Case Reports May 2024A male patient in his 40s who had been unwell for months with fever of unknown origin and clinicopathological features suspicious for haemophagocytic lymphohistiocytosis...
A male patient in his 40s who had been unwell for months with fever of unknown origin and clinicopathological features suspicious for haemophagocytic lymphohistiocytosis presented to hospital with worsening subacute shortness of breath. CT pulmonary angiogram demonstrated ground glass changes involving all lung lobes with an apicobasal gradient. These changes, combined with long-term steroid exposure for granulomatous hepatitis without pneumocystis prophylaxis, raised concern for pneumocystis jirovecii pneumonia (PJP). A subsequent bronchoscopic lavage specimen was positive on PCR for PJP and the patient was started on appropriate therapy. Clinical and radiological changes initially improved but after completion of therapy, symptoms and radiological abnormalities returned. Retreatment with second-line treatment resulted again in initial improvement followed by relapse with acute deterioration. Further investigations for an alternate diagnosis were made, with a surgical lung biopsy performed finally revealing immunosuppression-related Epstein-Barr virus positive large B cell lymphoma with lymphomatoid granulomatosis of grade 3 pattern.
Topics: Humans; Lymphomatoid Granulomatosis; Male; Diagnosis, Differential; Adult; Pneumonia, Pneumocystis; Pneumocystis carinii; Tomography, X-Ray Computed; Lung
PubMed: 38821563
DOI: 10.1136/bcr-2024-259969 -
The Lancet. Oncology Jun 2024
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Bridged Bicyclo Compounds, Heterocyclic; Sulfonamides; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38821078
DOI: 10.1016/S1470-2045(24)00260-2