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KMT2A (alias: mixed-lineage leukemia [MLL]) gene mapping on chromosome 11q23 encodes the lysine-specific histone N-methyltransferase 2A and promotes transcription by inducing an open chromatin conformation. Numerous genomic breakpoints within the KMT2A gene have been reported in young children and adults with hematologic disorders and are present in up to 10% of acute leukemias. These rearrangements describe distinct features and worse prognosis depending on the fusion partner, characterized by chemotherapy resistance and high rates of relapse, with a progression-free survival of 30–40% and overall survival below 25%. Less intensive regimens are used in pediatric patients, while new combination therapies and targeted immunotherapeutic agents are being explored in adults. Beneficial therapeutic effects, and even cure, can be reached with hematopoietic stem cell transplantation, mainly in young children with dismal molecular lesions; however, delayed related toxicities represent a concern. Herein, we summarize the translocation partner genes and partial tandem duplications of the KMT2A gene, their molecular impact, clinical aspects, and novel targeted therapies. [ABSTRACT FROM AUTHOR]

The correction notice in the International Journal of Molecular Sciences addresses errors in the original publication regarding KMT2A rearrangements in infant acute lymphoblastic leukemia (ALL). The correction clarifies that KMT2A rearrangements in infant ALL are somatic, not constitutive or inherited, and constitute the driver genetic alteration in 80% of acute leukemias during infancy. The correction also highlights the genetic enrichment in NUTM1 and PAX5 rearrangements in cases not involving KMT2A, with NUTM1 rearrangements showing a favorable prognosis compared to other gene rearrangements. The scientific conclusions of the study remain unaffected by the correction. [Extracted from the article]

Richter's syndrome represents the progression of chronic lymphocytic leukemia (CLL) to more aggressive diseases, most frequently diffuse large B-cell lymphoma, while Hodgkin's lymphoma (HL) and hairy cell leukemia (HCL) are rarely described. The first case involved a 67-year-old man with a diagnosis of a high-risk stage-II CLL treated with rituximab and ibrutinib, developed a HL nodular sclerosis variant after three months of therapy for CLL. After achieving a complete remission for HL and ibrutinib cessation because of drug-related cardiotoxicity, the patient relapsed after five months off-therapy and died due to disease progression after two cycles of brentuximab-vedotin. The second case involved an 83-year-old female with a diagnosis of stage-IV CLL treated with rituximab plus bendamustine who developed a HCL eight years later. Pentostatin was unsuccessfully employed as upfront HCL therapy, and the patient was then switched to rituximab while in remission for CLL. In conclusion, Richter's transformation risk rate might be higher in patients treated with novel targeted therapies, and multiparametric flow cytometry and lymph node biopsy at relapse could help in early identifying small clones. The treatment of predominant neoplasia is mandatory, and disease-specific drugs are administered; however, clinical efficacy might be lower in these patients. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma is associated with immunosuppression and human herpesvirus 8 infection, while rarely described in myeloid malignancies. Here, we illustrate a rare case of chronic myeloid leukemia treated with imatinib, a tyrosine kinase inhibitor, who developed a human herpesvirus 8‐related Kaposi's sarcoma. [ABSTRACT FROM AUTHOR]

Brentuximab-vedotin (BV)-induced neurotoxicity (BVIN), a frequent adverse event caused by this monoclonal antibody, is the primary reason for dose modification or drug discontinuation, and is characterized by sensory, motor, and/or autonomic peripheral nerve dysfunctions. Although reversible, BVIN can persist for months or years after treatment and negatively affect quality of life (QoL). Currently, BVIN is managed by dose adjustment or drug interruption, leading to an increased risk of disease relapse. Therefore, early recognition and appropriate management are essential to improve clinical outcomes. In this real-life study, we identified predictive factors for moderate/severe BVIN to reduce the risk of irreversible neuropathy. A total of 22 patients treated with BV were enrolled and BVIN was monitored by electro-neurography and neurological examinations every 2 cycles of therapy, while QoL by clinical questionnaires. We showed that recovery rate from moderate/severe BVIN was low, and sensory nerves were the most affected, negatively impacting QoL. BV dose reduction based on interim PET re-evaluation in patients with hematological response resulted in a significant reduction of BVIN onset with high long-term QoL. Therefore, electrophysiological tests could be useful tools to prevent moderate/severe BVIN onset, and their combination with interim PET imaging could allow dosage adjustments thus simultaneously minimizing risks of disease relapse and BVIN development. However, further studies on larger prospective randomized cohorts are needed to confirm our preliminary results., (© 2025 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)