STXBP2 (Syntaxin Binding Protein 2)

P1/2, N=10, Active, not recruiting, St. Jude Children's Research Hospital | Trial primary completion date: Aug 2025 --> Nov 2025

PML also occurs as a serious adverse event for a subset of immunosuppressive therapies (e.g., natalizumab and rituximab) used to treat patients with immune disorders (e.g., multiple sclerosis and hematological malignancies). Interestingly, of the 4 genes with a PML risk variant, 2 (LY9 and STXBP2) cause or are linked to HLH. The aim of our review is two-fold: (1) raise awareness among researchers and clinicians (e.g., neurologists, oncologists, and rheumatologists) that patient genetics are a key risk factor for PML, and (2) further reinforce the rationale for screening at-risk patients for PML risk variants before prescribing a PML-linked drug.

Patients with FHL-related germline mutations exhibited a trend towards better overall survival. In conclusion, germline mutations in FHL-related genes, particularly UNC13D, may contribute to PTCL susceptibility in Chinese patients and are associated with clonal somatic mutations.

This study presents a novel, comprehensive approach to endometrial cancer prognosis, integrating machine learning and molecular insights to provide a more precise risk stratification tool with potential clinical translation.

P1/2, N=10, Active, not recruiting, St. Jude Children's Research Hospital | N=62 --> 10

P1/2, N=62, Active, not recruiting, St. Jude Children's Research Hospital | Suspended --> Active, not recruiting

P1/2, N=62, Suspended, St. Jude Children's Research Hospital | Recruiting --> Suspended

In this study, we report the identification of 38 disease-causing variants, including 16 novel ones, detected in 40 patients across 15 distinct PIRD genes. The application of next-generation sequencing enabled rapid and precise diagnosis of patients with PIRDs.

Infection was identified in 8 of 9 patients: adenovirus, HHV6, EBV, and Streptococcus Group A. Only 2 patients received HLH-2004 therapy (dexamethasone, etoposide, cyclosporin-A) and the others received dexamethasone and/or intravenous gamma globulins (IVIG), with rapid resolution of fever (median 2 days). Early intervention with corticosteroids and/or IVIG may prevent deterioration, spare them from chemotherapy and provide time for more elaborate testing to identify true HLH. Unfortunately, mortality remains a significant risk for these children.

It was possible that impaired cytotoxic lymphocyte-mediated immune surveillance and autoantigen stimulation may both participate in PTCL oncogenesis. Germline defects of FLH-related genes may represent a novel predisposing factor for PTCLs.

This is the largest aggregated study of nHLH presentations, diagnostic criteria, clinical trajectory, and etiologic diagnoses. Neurologic, dermatologic, and hepatic manifestations occur in the neonatal population. Current reports of nHLH suggest a grim prognosis.

The blockade of interleukine-1 (anakinra and canakinumab) is a well-known highly effective tool for monogenic autoinflammatory diseases (AIDs), such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, hyperimmunoglobulinaemia D syndrome, and cryopyrin-associated periodic syndrome, but this treatment has not been assessed for patients with undifferentiated AIDs (uAIDs)...Initial treatment before canakinumab consisted of non-biologic therapies: non-steroidal anti-inflammatory drugs (NSAID) (91%), corticosteroids (88%), methotrexate (38%), intravenous immunoglobulin (IVIG) (34%), cyclosporine A (25%), colchicine (6%) cyclophosphamide (6%), sulfasalazine (3%), mycophenolate mofetil (3%), hydroxychloroquine (3%), and biologic drugs: tocilizumab (62%), sarilumab, etanercept, adalimumab, rituximab, and infliximab (all 3%)...The treatment of patients with uAIDs using canakinumab was safe and effective. Further randomized clinical trials are required to confirm the efficacy and safety.