MYD88 L265P

In conclusion, we uncovered new insights into the mutational landscape of WM, depicting a more complex involvement of the NF-kB pathway, and providing evidence of the recurrence of some variants (MYD88, IL17RB, NFKB2, ATM, CARD11, PTPN13, and WNK2) also in IgM MGUS.

Key concepts in the diagnosis and their clinical implications are emphasized. Controversies and challenges are also discussed.

Indeed, no structural variations or copy number alterations involving PD-1 ligands were detected by targeted-capture sequencing and fluorescence in situ hybridization. While further studies are warranted, we may have confirmed similarity between PCNS-LBCLs and intravascular large B-cell lymphomas from a molecular standpoint.

Uni- and multi-variate analyses of clinical variables that may be associated with clinical and MRD outcomes are underway.Conclusions : Bendamustine, rituximab and acalabrutinib front-line therapy for WM is safe and well tolerated in a relatively elderly population with a toxicity profile consistent with the utilized drugs and not greater than that seen with BR and Placebo in the randomized ECHO trial in untreated Mantle Cell Lymphoma. Initial clinical results show that this treatment is associated with a very high proportion of CR + VGPRs as well as MRD negativity.

This association will assist in identifying a target population that may benefit from MYD88-specific treatment regimens. This may exponentially improve the outcome of patients with DLBCL harboring this mutation.

Additionally, MYD88 L265P mutation was confirmed using Sanger sequencing in both samples, suggesting the MCD type. Our case highlights a discrepancy between the Hans' criteria and the gene expression profile-based cell of origin.

Lasalocid-A exhibited strong antitumor efficacy in xenograft mouse models, induced disease remission in ibrutinib-resistant lymphomas, and showed synergistic activity with the BCL2 inhibitor venetoclax. This study highlights the potential of inducing MYD88 L265P degradation using small molecules, offering promising strategies for treating lymphomas that harbor the MYD88 L265P mutation.

The relative survival (RS) ratio at 5 years of asymptomatic patients was similar to the Spanish population, which contrasted with the 0.76 5-year RS of SWM patients. Overall, the Spanish Multicenter Model comprehensively describes the risk of progression of asymptomatic patients and shows that the excess mortality is increased only in the symptomatic stage of the disease.

In conclusion, our study highlights a high prevalence of MYD88 and CD79B mutations in PSDLBCL, identifying an aggressive MCD-like subtype with a distinct relapse pattern. This molecular subclassification can be helpful for both prognostic prediction and therapeutic strategy in patients with PSDLBCL.

With a median follow-up of 73 months, the median TTNT in patients with and without CAs was 27 and 68 months, respectively. CAs with CBA may be associated with clinical aggressiveness and shorter TTNT in sWM.

Our findings indicate a high frequency of MYD88 L265P mutations in our study population and not associated with prognostic markers or the outcome of the disease.

However, we observed a subgroup of patients classified as BN2, both in localized and disseminated TLBCL, suggesting a degree of genetic heterogeneity in the TLBCL genetic profile. TLBCL has a distinctive genetic profile similar to PCNSL, supporting its recognition as a separate entity from DLBCL and might provide information to devise targeted therapeutic approaches.