PCM1 (Pericentriolar Material 1)

Our patient carried two acquired molecular abnormalities involving JAK2 gene (PCM1::JAK2 fusion and JAK2 H531Y) along with a germline mutation (BLM Y736fs*5, variant allele frequency VAF 41.7%), whereas his sister had the canonical JAK2 V617F driver mutation. This particular pedigree could arise the hypothesis of a genetic predisposition to acquire different JAK2 molecular abnormalities as a maladaptive somatic genetic rescue of an underlying germline predisposition, namely the germline BLM Y736fs*5 mutation.

Our findings highlight the potential of lactylation-associated genes, particularly XRCC4, in BC progression and clinical treatment strategies. The development of an XRCC4 inhibitor may be eligible for patent protection and could potentially serve as a novel therapeutic option for BC.

The case highlights the importance of distinguishing de novo lymphoid malignancies from MLN-eo-TK, especially when JAK2 rearrangements are detected. Recognition of the clonal myeloid component during or after lymphoid-directed therapy has important diagnostic and therapeutic implications, supporting the use of targeted JAK2 inhibition in addition to standard chemotherapy.

Multi-omics analysis suggests that PCMT1 may serve as a potential prognostic biomarker and a novel immunotherapy target for pan-cancer.

P2, N=10, Recruiting, William Shomali | Trial completion date: Nov 2025 --> Dec 2028 | Trial primary completion date: Nov 2025 --> Dec 2028

Despite partial responses to topical therapies, oral prednisone, and methotrexate, the disease persisted, highlighting therapeutic challenges. This case underscores the importance of molecular profiling in PCAECTCL and suggests potential utility for JAK inhibitors like ruxolitinib.

This case series found that JAK2 fusions were seen in aggressive cytotoxic CTCL as well as in T-cell lymphomas with more indolent behavior, possibly representing a precursor lesion to aggressive evolution with age and comorbidities. The prominence of these fusions supports a potentially larger role for JAK2 targeting in patients with early-stage MF, CD30-positive LPD, or overlap presentations.

Complexes [RuCp(PPh3)2(HdmoPTA)][PtCl4] (1), [RuCp(PPh3)2-µ-dmoPTA-1κP:2κ2-N,N'-Pt(κ2 C,O-CH2N(CH3)CHO)][PtCl4] (2), [RuClCp(PPh3) (HdmoPTA)]2[PtCl4] (3), and [RuClCp(PPh3)-µ-dmoPTA-1κP:2κ2-N,N'-Pt(κ2 C,O-CH2N(CH3)CHO)]2[PtCl4] (4) have been synthesized and characterized by NMR, IR, and crystal structure of 2 was obtained by single crystal X-Ray diffraction. Antiproliferative activity of 1 was assessed against six human solid tumor cell lines and compared to cisplatin as a standard, showing GI50 values in the submicromolar range.

Treatment was heterogeneous, although usually included narrowband UVB phototherapy for MF, and topical steroids for MF and LyP. We demonstrate that pediatric MF, LyP, and pcALCL harbor frequent tyrosine kinase gene fusions with enrichment of JAK2 and TYK2 fusions, genomic alterations that are diagnostically useful and may be amenable to targeted therapy.

The absence of the CC domains 5-7 in mutant spermatids destabilizes PCM1, which fails to recruit satellite components such as Bardet-Biedl syndrome 4 (BBS4) and centrosomal protein of 131 kDa (CEP131) to satellites, resulting in defective sperm flagellum biogenesis, as BBS4 and CEP131 are essential to flagellum biogenesis. In conclusion, this study reveals the central role of SDCCAG8 in maintaining centriolar satellite integrity during sperm flagellum biogenesis.

These findings identify BAP31 as a regulator of the Hippo pathway, highlighting its critical role in breast cancer tumorigenesis and stemness. Consequently, BAP31 emerges as a potential therapeutic target for this malignancy.