Mutations in SF3B1 are found in 20% of myelodysplastic syndromes and 5–10% of myeloproliferative neoplasms, where they are considered important for diagnosis and therapy decisions. Sanger sequencing and NGS are the currently available methods to identify SF3B1 mutations, but both are time-consuming and expensive techniques that are not practicable in most small-/medium-sized laboratories. To identify the most frequent SF3B1 mutation, p.Lys700Glu, we developed a novel fast and cheap assay based on PNA-PCR clamping. After setting the optimal PCR conditions, the limit of detection of PNA-PCR clamping was evaluated, and the method allowed up to 0.1% of mutated SF3B1 to be identified. Successively, PNA-PCR clamping and Sanger sequencing were used to blind test 90 DNA from patients affected by myelodysplastic syndromes and myeloproliferative neoplasms for the SF3B1 p.Lys700Glu mutation. PNA-PCR clamping and Sanger sequencing congruently identified 75 negative and 13 positive patients. Two patients identified as positive by PNA-PCR clamping were missed by Sanger analysis. The discordant samples were analyzed by NGS, which confirmed the PNA-PCR clamping result, indicating that these samples contained the SF3B1 p.Lys700Glu mutation. This approach could easily increase the characterization of myelodysplastic syndromes and myeloproliferative neoplasms in small-/medium-sized laboratories, and guide patients towards more appropriate therapy.

Background: Recurrence, even after years from the last treatment, characterizes lymphoproliferative disorders. Therefore, patients in complete remission from the disease should be followed up with periodic clinical checks. There is not a consensus on the role of imaging for this aim, because the radiological techniques used at the time of diagnosis expose patients to a risk of ionizing radiation damage. Whole-body magnetic resonance imaging with diffusion-weighted imaging (WB-MRI-DWI) has given similar results to gold standard techniques in detecting lymphoma in the involved sites without ionizing radiation. In this retrospective real-life study, we aimed to assess the accuracy of WB-MRI-DWI during follow-ups of lymphoma patients in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Methods: Lymphoma patients who were subject to at least one WB-MRI-DWI during follow-up between February 2010 and February 2022 were enrolled. Results: Based on our investigation, the calculated sensitivity of WB-MRI-DWI was 100% (95% CI: 99.4–100.0), the specificity was 98.6% (95% CI: 97.4–99.3), PPV was 79% (95% CI: 75.9–81.9), and NPV was 100% (95% CI: 99.4–100.0). Conclusions: Despite the possibility of poor patient compliance and the identification of false positives, WB-MRI-DWI examination demonstrated an excellent sensitivity in ruling out the disease relapse.

Background: Ibrutinib, a Bruton’s tyrosine kinase inhibitor (BTKi), has revolutionized the treatment of Chronic Lymphocytic Leukemia (CLL), yet hepatotoxicity remains a rare and poorly characterized adverse event. Case Presentation: We report the case of a 54-year-old man with progressive CLL and radiologically confirmed hepatic involvement who developed acute hepatocellular injury during ibrutinib monotherapy. Baseline liver tests showed mild abnormalities attributed to hepatic steatosis and leukemic infiltration. After approximately 10–12 weeks of ibrutinib (420 mg/day), transaminases markedly increased (ALT 660 U/L, AST 326 U/L), while bilirubin and synthetic function remained normal. Viral, autoimmune, and obstructive causes were excluded. Stepwise dose reductions to 140 mg/day provided limited benefit. The addition of prednisone (50 mg/day) led to rapid biochemical improvement. Ibrutinib was successfully re-escalated to 280 mg/day alongside venetoclax initiation, maintaining disease control without recurrence of liver injury. Discussion: The temporal relationship, exclusion of alternative causes, and corticosteroid responsiveness suggest an ibrutinib-induced liver injury, possibly exacerbated by pre-existing hepatic steatosis and leukemic infiltration. Conclusions: This case underscores the multifactorial pathogenesis of BTKi-related hepatotoxicity and highlights the potential role of corticosteroids in management. Prompt recognition, stepwise dose adjustment, and corticosteroid therapy may enable continued treatment and sustained disease control in selected patients.

Interferons (IFNs) are pleiotropic cytokines involved in antiviral defense, immune regulation, and tumor suppression. In myeloproliferative neoplasms (MPNs) and related disorders—including classical BCR, ABL1-negative MPNs, chronic myeloid leukemia (CML), and rarer entities such as chronic neutrophilic leukemia and hypereosinophilic syndromes—disease pathogenesis arises from a spectrum of somatic and structural genetic abnormalities and chronic inflammation, in which IFNs play a paradoxical role. They contribute to disease pathogenesis by promoting abnormal hematopoiesis and immune dysregulation, while also representing a therapeutic option capable of inducing hematologic and molecular remissions. This review outlines the biology and classification of IFNs, focusing on their signaling pathways and downstream effects in both normal and malignant hematopoiesis. We discuss the dual impact of IFN signaling on hematopoietic stem cells, including induction of proliferation, senescence, apoptosis, and DNA damage, and how these mechanisms may both sustain clonal evolution and facilitate disease control. Clinical data supporting the efficacy and safety of IFN-α, particularly pegylated formulations, in polycythemia vera, essential thrombocythemia, myelofibrosis, and chronic myeloid leukemia are reviewed, along with insights into next-generation IFNs and combination therapies. Understanding the dichotomous effects of IFNs in MPNs not only clarifies their role in disease biology but also informs their optimal use in clinical practice. This duality highlights the need for personalized approaches to IFN-based therapies.

The FLT3-ITD mutation is a critical prognostic marker in acute myeloid leukemia (AML) and recent clinical trials demonstrate that FLT3-based measurable residual disease (MRD) is both prognostic and predictive, guiding therapeutic interventions in intensive and post-transplant settings. Conventional detection methods lack the sensitivity required for effective MRD monitoring. We developed a patient-specific droplet digital PCR (ddPCR) approach achieving analytical sensitivity of 10⁻⁵ (0.001%) for FLT3-ITD quantification. In our cohort, ddPCR enabled longitudinal monitoring of clonal dynamics, allowing the detection of re-emerging FLT3-ITD clones months before hematologic relapse and earlier than standard capillary electrophoresis. Notably, 25% of patients who relapsed as FLT3-ITD positive despite being classified as FLT3-negative at diagnosis harbored detectable microclones when retrospectively analyzed by ddPCR, suggesting that FLT3-ITD-positive relapse frequently originates from pre-existing subclones below conventional detection thresholds. These findings challenge current diagnostic classification and may influence risk stratification and treatment decisions, particularly regarding FLT3 inhibitor eligibility. While ddPCR is limited to tracking known dominant clones, it represents a practical, cost-effective solution for high-sensitivity MRD surveillance. In the era of targeted FLT3 therapies, integrating sensitive molecular monitoring into routine AML management may enable timely therapeutic adjustments and improve patient outcomes.

While systemic mastocytosis (SM) is well-established in its association with myeloid neoplasms, its concurrent occurrence with lymphoproliferative disorders is exceedingly rare and poorly characterized. We report a multicenter retrospective series of 9 patients diagnosed with both SM and lymphoma according to WHO 2022 criteria.