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Journal of Investigational Allergology... Jun 2024
Successful Desensitization to Isatuximab in a Patient With Refractory Multiple Myeloma and Indolent Systemic Mastocytosis. Reply to: Anaphylactic Shock due to Isatuximab and Successful Desensitization.
Topics: Humans; Multiple Myeloma; Anaphylaxis; Mastocytosis, Systemic; Desensitization, Immunologic; Antibodies, Monoclonal, Humanized; Drug Hypersensitivity
PubMed: 38888584
DOI: 10.18176/jiaci.0990 -
Journal of the National Comprehensive... Jun 2024Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of...
Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of symptoms related to the release of mast cell mediators and mast cell tissue infiltration. Referral to specialized centers with expertise in the management of mastocytosis and multidisciplinary collaboration with subspecialists (eg, allergists for the management of anaphylaxis and drug hypersensitivities, anesthesiologists for invasive procedures or surgery, high-risk obstetrician for pregnancy) is recommended. The NCCN Guidelines for Systemic Mastocytosis provide evidence- and consensus-based recommendations for the diagnosis and comprehensive care of patients with systemic mastocytosis. The multidisciplinary panel of experts convenes at least once a year to review requested changes to the guidelines from both internal and external entities as well as to discuss data on existing and new therapies. These NCCN Guidelines Insights focus on some of the recent updates to the guidelines.
Topics: Humans; Mastocytosis, Systemic; Disease Management; Medical Oncology
PubMed: 38862005
DOI: 10.6004/jnccn.2024.0030 -
Current Opinion in Allergy and Clinical... Aug 2024Patients with mast cell disorders frequently experience symptoms from excessive mediator release like histamine and tryptase, ranging from mild flushing to severe... (Review)
Review
PURPOSE OF REVIEW
Patients with mast cell disorders frequently experience symptoms from excessive mediator release like histamine and tryptase, ranging from mild flushing to severe anaphylactic responses. Hypersensitivity reactions (HRs) to drugs are a major cause of anaphylaxis in these patients, who often worry about triggering mast cell degranulation when taking medications. The aim of this review is to explore the complex interactions between mast cell disorders and drug HRs, focusing on the clinical challenges of managing these conditions effectively to enhance understanding and guide safer clinical practices.
RECENT FINDINGS
Among the drugs most commonly associated with hypersensitivity reactions in patients with mast cell disorders are non-steroidal anti-inflammatory drugs, antibiotics, and perioperative agents. Recent studies have highlighted the role of Mas-related G-protein coupled receptor member X2 (MRGPRX2) - a receptor involved in non-immunoglobulin E mediated mast cell degranulation - in exacerbating HRs. Investigations reveal varied drug tolerance among patients, underscoring the need for individual risk assessments.
SUMMARY
Tailored diagnostic approaches are crucial for confirming drug allergies and assessing tolerance in patients with mastocytosis, preventing unnecessary medication avoidance and ensuring safety before acute situations arise.
Topics: Humans; Mast Cells; Drug Hypersensitivity; Receptors, G-Protein-Coupled; Anaphylaxis; Receptors, Neuropeptide; Cell Degranulation; Mastocytosis; Anti-Inflammatory Agents, Non-Steroidal; Animals; Anti-Bacterial Agents; Nerve Tissue Proteins
PubMed: 38814742
DOI: 10.1097/ACI.0000000000001001 -
Cells Apr 2024The unfolded protein response is an intricate system of sensor proteins in the endoplasmic reticulum (ER) that recognizes misfolded proteins and transmits information...
TurboID-Based IRE1 Interactome Reveals Participants of the Endoplasmic Reticulum-Associated Protein Degradation Machinery in the Human Mast Cell Leukemia Cell Line HMC-1.2.
The unfolded protein response is an intricate system of sensor proteins in the endoplasmic reticulum (ER) that recognizes misfolded proteins and transmits information via transcription factors to either regain proteostasis or, depending on the severity, to induce apoptosis. The main transmembrane sensor is IRE1α, which contains cytoplasmic kinase and RNase domains relevant for its activation and the mRNA splicing of the transcription factor XBP1. Mast cell leukemia (MCL) is a severe form of systemic mastocytosis. The inhibition of IRE1α in the MCL cell line HMC-1.2 has anti-proliferative and pro-apoptotic effects, motivating us to elucidate the IRE1α interactors/regulators in HMC-1.2 cells. Therefore, the TurboID proximity labeling technique combined with MS analysis was applied. Gene Ontology and pathway enrichment analyses revealed that the majority of the enriched proteins are involved in vesicle-mediated transport, protein stabilization, and ubiquitin-dependent ER-associated protein degradation pathways. In particular, the AAA ATPase VCP and the oncoprotein MTDH as IRE1α-interacting proteins caught our interest for further analyses. The pharmacological inhibition of VCP activity resulted in the increased stability of IRE1α and MTDH as well as the activation of IRE1α. The interaction of VCP with both IRE1α and MTDH was dependent on ubiquitination. Moreover, MTDH stability was reduced in IRE1α-knockout cells. Hence, pharmacological manipulation of IRE1α-MTDH-VCP complex(es) might enable the treatment of MCL.
Topics: Humans; Cell Line, Tumor; Endoplasmic Reticulum-Associated Degradation; Endoribonucleases; Leukemia, Mast-Cell; Membrane Proteins; Protein Serine-Threonine Kinases; Valosin Containing Protein
PubMed: 38727283
DOI: 10.3390/cells13090747 -
Experimental Dermatology May 2024KIT ligand and its associated receptor KIT serve as a master regulatory system for both melanocytes and mast cells controlling survival, migration, proliferation and... (Review)
Review
KIT ligand and its associated receptor KIT serve as a master regulatory system for both melanocytes and mast cells controlling survival, migration, proliferation and activation. Blockade of this pathway results in cell depletion, while overactivation leads to mastocytosis or melanoma. Expression defects are associated with pigmentary and mast cell disorders. KIT ligand regulation is complex but efficient targeting of this system would be of significant benefit to those suffering from melanocytic or mast cell disorders. Herein, we review the known associations of this pathway with cutaneous diseases and the regulators of this system both in skin and in the more well-studied germ cell system. Exogenous agents modulating this pathway will also be presented. Ultimately, we will review potential therapeutic opportunities to help our patients with melanocytic and mast cell disease processes potentially including vitiligo, hair greying, melasma, urticaria, mastocytosis and melanoma.
Topics: Humans; Stem Cell Factor; Melanocytes; Mast Cells; Mastocytosis; Proto-Oncogene Proteins c-kit; Melanoma; Vitiligo; Pigmentation Disorders; Skin Neoplasms; Animals
PubMed: 38711220
DOI: 10.1111/exd.15091 -
Orvosi Hetilap May 2024
Topics: Humans; Mastocytosis, Systemic; Diarrhea; Mast Cells
PubMed: 38709596
DOI: 10.1556/650.2024.33040 -
British Journal of Haematology May 2024Systemic mastocytosis (SM) is a rare haematological neoplasm associated with the gain of function mutation KIT D816V in 90% of adult patients. Classically, cytogenetic...
Systemic mastocytosis (SM) is a rare haematological neoplasm associated with the gain of function mutation KIT D816V in 90% of adult patients. Classically, cytogenetic aberrations are not common except in cases of SM associated with another haematological neoplasm. We highlight here an unusual clinical presentation of SM and demonstrate the utility of advanced cytogenetic analysis (optical genome mapping, OGM) in detecting a novel cytogenetic abnormality resulting in an unusual mechanism of DNMT3A and TET2 loss of function.
PubMed: 38702998
DOI: 10.1111/bjh.19501 -
Blood May 2024
Topics: Humans; Male; Middle Aged; Mastocytosis, Systemic; Myelolipoma
PubMed: 38696191
DOI: 10.1182/blood.2024023917 -
Hematological Oncology May 2024
Comparative Study
Topics: Humans; Mastocytosis, Systemic; Retrospective Studies; Male; Female; Middle Aged; Aged; World Health Organization; Adult
PubMed: 38682493
DOI: 10.1002/hon.3277 -
Cytometry. Part B, Clinical Cytometry Apr 2024Flow cytometry has been widely used to study immunophenotypic patterns of maturation of most hematopoietic lineages in normal human bone marrow aspirates, thus allowing...
BACKGROUND
Flow cytometry has been widely used to study immunophenotypic patterns of maturation of most hematopoietic lineages in normal human bone marrow aspirates, thus allowing identification of changes in patterns in many myeloid malignancies. Eosinophils play an important role in a wide variety of disorders, including some myeloid neoplasms. However, changes in flow cytometric immunophenotypic patterns during normal and abnormal bone marrow eosinophilopoiesis have not been well studied.
METHODS
Fresh bone marrow aspirates from 15 healthy donors, 19 patients with hypereosinophilic syndromes (HES), and 11 patients with systemic mastocytosis (SM) were analyzed for candidate markers that included EMR-1, Siglec-8, CCR3, CD9, CD11a, CD11b, CD11c, CD13, CD16, CD29, CD34, CD38, CD45, CD44, CD49d, CD49f, CD54, CD62L, CD69, CD117, CD125 (IL-5Rα), HLA-DR, using 10 parameter flow cytometry. Putative CD34-negative immature and mature normal eosinophil populations were first identified based on changes in expression of the above markers in healthy donors, then confirmed using fluorescence-based cell sorting and morphological evaluation of cytospin preparations. The normal immunophenotypic patterns were then compared to immunophenotypic patterns of eosinophilopoiesis in patients with HES and SM.
RESULTS
The eosinophilic lineage was first verified using the human eosinophil-specific antibody EMR-1 in combination with anti-IL-5Rα antibody. Then, a combination of Siglec-8, CD9, CD11b, CCR3, CD49d, and CD49f antibodies was used to delineate normal eosinophilic maturational patterns. Early stages (eosinophilic promyelocytes/myelocytes) were identified as Siglec-8 dim/CD11b dim to moderate/CD9 dim/CCR3 dim/CD49d bright/CD49f dim, intermediate stages (eosinophilic myelocytes/metamyelocytes) as Siglec-8 moderate/CD11b moderate to bright/CD9 moderate/CCR3 moderate/CD49d moderate/CD49f moderate and mature bands/segmented eosinophils as Siglec-8 bright/CD11b bright/CD9 bright/CCR3 bright/CD49d dim/CD49f bright. Overall maturational patterns were also similar in patients with HES and SM; however, the expression levels of several surface markers were altered compared to normal eosinophils.
CONCLUSION
A novel flow cytometric antibody panel was devised to detect alterations in immunophenotypic patterns of bone marrow eosinophil maturation and evaluated in normal, HES and SM samples. This approach will allow us to elucidate changes in immunophenotypic patterns of bone marrow eosinophilopoiesis in other hematological diseases.
PubMed: 38666394
DOI: 10.1002/cyto.b.22174