A novel t(X;21)(p11.4;q22.12) translocation adds to the role of BCOR and RUNX1 in myelodysplastic syndromes and acute myeloid leukemias.

In myeloid neoplasms, both fusion genes and gene mutations are well-established events identifying clinicopathological entities. In this study, we present a thus far undescribed t(X;21)(p11.4;q22.12) in five cases with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The translocation was isolated or accompanied by additional changes. It did not generate any fusion gene or gene deregulation by aberrant juxtaposition with regulatory sequences. Molecular analysis by targeted next-generation sequencing showed that the translocation was accompanied by at least one somatic mutation in TET2, EZH2, RUNX1, ASXL1, SRSF2, ZRSR2, DNMT3A, and NRAS genes. Co-occurrence of deletion of RUNX1 in 21q22 and of BCOR in Xp11 was associated with t(X;21). BCOR haploinsufficiency corresponded to a significant hypo-expression in t(X;21) cases, compared to normal controls and to normal karyotype AML. By contrast, RUNX1 expression was not altered, suggesting a compensatory effect by the remaining allele. Whole transcriptome analysis showed that overexpression of HOXA9 differentiated t(X;21) from both controls and t(8;21)-positive AML. In conclusion, we characterized a new recurrent reciprocal t(X;21)(p11.4;q22.12) chromosome translocation in MDS and AML, generating simultaneous BCOR and RUNX1 deletions rather than a fusion gene at the genomic level.

Mast Cell Leukemia: An Update with a Practical Review.

Mast cell leukemia (MCL) is the leukemic form of SM with at least 20% mostly immature mast cells on bone marrow aspirate. MCL may develop de novo, in the absence of a prior SM, or it may represent a progression from a previous SM. MCL may be sub-divided into the more frequent, aggressive acute form with signs of organ damage (C-findings) and the chronic form lacking C-findings and presenting a more stable course, although over time, progression to acute MCL is common. The 2022 WHO subtype of MCL with an associated hematological neoplasm was renamed MCL with an associated myeloid neoplasm in the 2022 International Consensus Classification (ICC). The relevance of the distinction between the leukemic and aleukemic forms based on the percentage of circulating mast cells is a matter of debate. The current knowledge on MCL is restricted mainly to single reports or case series with a limited number of larger studies. Our aim is to provide a comprehensive overview of this rare disease in terms of clinical manifestations, morphology, phenotype, molecular characteristics, differential diagnosis, outcome and treatment. A general overview on mastocytosis is also included.

Biomimetic Action of Zinc Hydroxyapatite on Remineralization of Enamel and Dentin: A Review.

Biomimetic zinc-carbonate hydroxyapatite technology was developed to realize materials that mimic the natural hydroxyapatite of enamel and dentin and possess good activity in terms of affinity to adhere to these biological tissues. The chemical and physical characteristics of this active ingredient allows the hydroxyapatite itself to be particularly similar to dental hydroxyapatite, enhancing the bond between biomimetic hydroxyapatite and dental hydroxyapatite. The aim of this review is to assess the efficacy of this technology in terms of benefits for enamel and dentin and reduction of dental hypersensitivity. MATERIALS AND METHODS: A literature search (Pubmed/MEDLINE and Scopus) of articles from 2003 to 2023 was conducted to analyze studies focused on the use of zinc-hydroxyapatite products. Duplicates were eliminated from the 5065 articles found, leaving 2076 articles. Of these, 30 articles were analyzed based on the use of products with zinc-carbonate hydroxyapatite in these studies. RESULTS: 30 articles were included. Most of the studies showed benefits in terms of remineralization and prevention of enamel demineralization in terms of occlusion of the dentinal tubules and reduction of dentinal hypersensitivity. CONCLUSION: Oral care products such as toothpaste and mouthwash with biomimetic zinc-carbonate hydroxyapatite were shown to provide benefits according to the aims of this review.

Myelodysplastic/myeloproliferative neoplasm with neutrophilia (atypical chronic myeloid leukemia-aCML).

A case of myelodysplastic/myeloproliferative neoplasm with neutrophilia (aCML) with SETBP1 and ASXL1 mutations.

Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults.

Chromothripsis is a mitotic catastrophe that arises from multiple double strand breaks and incorrect re-joining of one or a few chromosomes. We report on incidence, distribution, and features of chromothriptic events in T-cell acute lymphoblastic leukemias (T-ALL). SNP array was performed in 103 T-ALL (39 ETP/near ETP, 59 non-ETP, and 5 with unknown stage of differentiation), including 38 children and 65 adults. Chromothripsis was detected in 11.6% of all T-ALL and occurred only in adult cases with an immature phenotype (12/39 cases; 30%). It affected 1 to 4 chromosomes, and recurrently involved chromosomes 1, 6, 7, and 17. Abnormalities of genes typically associated with T-ALL were found at breakpoints of chromothripsis. In addition, it gave rise to new/rare alterations, such as, the SFPQ::ZFP36L2 fusion, reported in pediatric T-ALL, deletions of putative suppressors, such as IKZF2 and CSMD1, and amplification of the BCL2 gene. Compared to negative cases, chromothripsis positive T-ALL had a significantly higher level of MYCN expression, and a significant downregulation of RGCC, which is typically induced by TP53 in response to DNA damage. Furthermore we identified mutations and/or deletions of DNA repair/genome stability genes in all cases, and an association with NUP214 rearrangements in 33% of cases.

Visceral Leishmaniasis Associated with B-Cell Chronic Lymphocytic Leukemia: Report of a Case and Review of the Literature.

Infections often complicate the course of hematological diseases and may represent a diagnostic challenge. In particular, visceral leishmaniasis diagnosis may be missed in lymphoma patients, as lymphoma-related immunosuppression can lead to a misleadingly negative Leishmania serology and to atypical clinical manifestations, including the lack of fever, considered a common symptom in leishmaniasis. Herein, we report a case of visceral leishmaniasis in a patient with a long history of B-cell chronic lymphocytic leukemia presenting with increasing fatigue and diarrhea, in the absence of fever. Leishmania serology was negative. Bone marrow biopsy performed with the clinical suspicion of transformation to high-grade lymphoma disclosed intracytoplasmic inclusion bodies resembling Leishmania amastigotes within the cytoplasm of macrophages, and CD1a immunohistochemical expression helped to confirm the diagnosis of leishmaniasis. Liposomal amphotericin B was administered with complete symptom resolution. The correct identification of Leishmania is critical as visceral leishmaniasis represents a severe disease with an often fatal outcome, particularly in frail patients, unless promptly recognized and adequately treated. A review of the literature of visceral leishmaniasis cases occurring in B-cell chronic lymphocytic leukemia patients is performed.

Genomic and clinical findings in myeloid neoplasms with PDGFRB rearrangement.

Platelet-derived growth factor receptor B (PDGFRB) gene rearrangements define a unique subgroup of myeloid and lymphoid neoplasms frequently associated with eosinophilia and characterized by high sensitivity to tyrosine kinase inhibition. To date, various PDGFRB/5q32 rearrangements, involving at least 40 fusion partners, have been reported. However, information on genomic and clinical features accompanying rearrangements of PDGFRB is still scarce. Here, we characterized a series of 14 cases with a myeloid neoplasm using cytogenetic, single nucleotide polymorphism array, and next-generation sequencing. We identified nine PDGFRB translocation partners, including the KAZN gene at 1p36.21 as a novel partner in a previously undescribed t(1;5)(p36;q33) chromosome change. In all cases, the PDGFRB recombination was the sole cytogenetic abnormality underlying the phenotype. Acquired somatic variants were mainly found in clinically aggressive diseases and involved epigenetic genes (TET2, DNMT3A, ASXL1), transcription factors (RUNX1 and CEBPA), and signaling modulators (HRAS). By using both cytogenetic and nested PCR monitoring to evaluate response to imatinib, we found that, in non-AML cases, a low dosage (100-200 mg) is sufficient to induce and maintain longstanding hematological, cytogenetic, and molecular remissions.

Flower cells of tropical descent: a challenging case of adult T-cell leukemia/lymphoma.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease associated with human T-lymphotropic virus type 1 infection, with a very high prevalence in tropical areas but exceptionally rare in Europe and Western countries. CASE PRESENTATION: We describe a challenging case of ATLL in a young male patient with Brazilian origin and adopted as a child by an Italian family, presenting to our clinic with atypical T-lymphocytosis and life-threatening lung infections. CONCLUSIONS: Diagnosis of ATLL outside of endemic areas can be difficult, requiring a high index of clinical suspicion with careful evaluation of the patient's clinical history. Prognosis is affected by disease stage at presentation and degree of immunosuppression. Few effective treatments are available, although new molecular insights have highlighted the role of host immune response and immune checkpoint blockade inhibitors, given the overexpression of PD-L1 on lymphoma cells and on microenvironment cells.