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Circular RNAs (circRNAs) are single-stranded RNAs that have received much attention in recent years. CircRNAs lack a 5’ head and a 3’ poly-A tail. The structure of this type of RNAs make them resistant to digestion by exonucleases. CircRNAs are expressed in different cells and have various functions. The function of circRNAs is done by sponging miRNAs, changing gene expression, and protein production. The expression of circRNAs changes in different types of cancers, which causes changes in cell growth, proliferation, differentiation, and apoptosis. Changes in the expression of circRNAs can cause the invasion and progression of tumors. Studies have shown that changes in the expression of circRNAs can be seen in acute lymphoid leukemia (ALL) and chronic lymphoid leukemia (CLL). The conducted studies aim to identify circRNAs whose expression has changed in these leukemias and their more precise function so that these circRNAs can be identified as biomarkers, prediction of patient prognosis, and treatment targets for ALL and CLL patients. In this study, we review the studies conducted on the role and function of circRNAs in ALL and CLL patients. The results of the studies show that there is a possibility of using circRNAs as biomarkers in the identification and treatment of patients in the future.

Clonal heterogeneity within chronic lymphocytic leukemia (CLL) has been increasingly recognized as a factor that may influence disease progression, treatment response, and prognosis. Here, we report a rare case of CLL with two distinct B-cell populations displaying distinct immunophenotypic characteristics, genetic mutations, and genetic evolution. The two aberrant mature B cell populations were identified in peripheral blood (PB) and bone marrow (BM) through multiparametric flow cytometry (MFC) with identical light chain restriction but distinct immunophenotypes. The first population (CD5 + CD23+CD200+) was consistent with typical CLL, while the second (CD5-CD23-CD200-) displayed atypical features. Further characterization through flow sorting, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) revealed that both populations shared the same BCL2-IgH translocation and an identical IGHV gene usage, but exhibited different IGHV mutation rates. NGS revealed that a common progenitor cell with BCL2-IgH translocation and mutations in TP53, KMT2A, KMT2C, and KMT2D gave rise to two distinct subclones: one (CD5 + CD23+CD200+) CLL driven by mutations in TNFAIP3 and BCORL1, and the other (CD5-CD23-CD200-) driven by mutations in EP300, NOTCH1, and BCL2. This case highlights the significance of clonal heterogeneity in CLL and underscores the crucial role of MFC, flow sorting, and molecular genetics in diagnosing and understanding the complex evolution of this disease.

Liquid biopsy is classically defined as the detection of biomarkers in bodily fluids. One of these biomarkers can be circulating cell-free DNA (cfDNA) released by healthy or cancer cells during apoptosis. These fragments can be quantified and molecularly characterized by techniques like digital droplet PCR (ddPCR) or next-generation sequencing (NGS). By identifying common genetic and epigenetic alterations associated with specific cancer types, cfDNA or circulating tumor DNA (ctDNA) can serve as robust biomarkers for monitoring tumor initiation and progression. Other biomarkers, such as circulating microRNAs (miRNAs), extracellular vesicles, or circulating tumor cells (CTCs) are also applied in this context. Liquid biopsy has gained attention as a versatile tool for cancer diagnostics, prognosis, therapeutic monitoring, and minimal residual disease (MRD) detection across various malignancies, including hematological cancers like myeloid and lymphoid leukemias. Herein, we present a comprehensive review of liquid biopsy usage in leukemia, with a specific focus on the clinical utility of ctDNA, miRNAs, and exosomes in monitoring treatment response, tracking clonal evolution, and detecting minimal residual disease. Our review emphasizes the translational implications of these tools for improving patient outcomes and outlines current challenges in their integration into clinical practice.

Background Despite advances in understanding the principles of leukemia biology and therapeutic achievements, older patients with leukemia continue to face serious challenges. Thus, the diagnosis, treatment, and management of geriatric people with leukemia continue to be significant worldwide health issues. Methods We gathered data on acute myeloid leukemia, acute lymphoid leukemia, chronic myeloid leukemia, and chronic lymphoid leukemia in older individuals (aged 60–89 years) from the Global Burden of Disease Study 2019. We investigated the epidemiological characteristics of leukemia in older people from 21 regions and 204 countries and territories, using measures of morbidity, mortality, and disability‐adjusted life‐years (DALYs). Furthermore, we used BAPC (Bayesian age‐period‐cohort) modeling to project leukemia incidence rates from 2019 to 2030 for older adults, broken down by sex. We also looked at risk factors for leukemia‐related DALYs and deaths. Results Over the past 3 decades, the incidence, mortality, and DALYs associated with leukemia have increased markedly among the global population of older adults. Although chronic myeloid leukemia showed a reduced incidence rate and a decrease in mortality and DALYs, the disease burden of other forms of leukemia continues to escalate to different degrees, shaped by regional and national determinants. Importantly, sociodemographic index was associated with variations in leukemia incidence, mortality, and DALYs. Smoking persisted as a substantial risk factor for leukemia‐related death. Projecting the incidence of leukemia in older adults from 2019 to 2030, the incidence of leukemia will remain on the rise and be higher in men than in women. Conclusions Overall, leukemia continues to pose a major threat to health and quality of life among older adults. There is a pressing need for all sectors to collaborate globally to develop individualized treatment plans and advocate for scientific advancements. After analyzing the burden of leukemia in the elderly aged 60–89 years from 1990 to 2019 using the Global Burden of Disease database, we found that although the burden of chronic myeloid leukemia has decreased over the past 30 years, the burden of other types of leukemia has continued to increase to varying degrees. Smoking remains an important risk factor for leukemia‐related deaths. It is projected that the incidence of leukemia will continue to rise by 2030, with a higher incidence rate among men than women.

OBJECTIVE:We studied the risk of 11 cancers of a priori interest in petroleum refinery workers. METHODS:Iterative searches identified 36 studies for the 11 cancer sites. Statistical heterogeneity and publication bias were assessed to enhance interpretation of meta-relative risks. RESULTS:Statistical heterogeneity was marked for mesothelioma, but was largely due to study quality. Higher quality studies showed a meta-relative risk (RR) of 3.22, (95% prediction interval 1.45 to 7.23). Melanoma (meta-RR = 1.23) and acute lymphoid leukemia (meta-RR = 1.51), showed results consistent with higher risk, but both were driven by one or two studies. Eight other cancer outcomes showed summary meta-RRʼs consistent with unity. CONCLUSIONS:Most cancer outcomes are consistent with background risk in refinery workers. This work has clarified an excess mesothelioma risk, conditional on study quality stratification. Continued surveillance is warranted for melanoma and ALL.

Background Chronic lymphoid leukemia (CLL) is a hematological disorder characterized by the clonal expansion of small mature lymphocytes that accumulate in the blood and bone marrow. CLL can arise from B-, T-, or natural killer cell clones. The cytological evaluation of blood smears is often the simplest and least invasive method for diagnosing lymphoid leukemia. Immunophenotyping is used to further subclassify the type of lymphoid leukemia. Case presentation A 15-year-old, 4.4-kg spayed female Shih Tzu was presented to the veterinary medical teaching hospital of Kangwon National University. Despite having a normal appetite and activity level, cervical and inguinal lymph node enlargement was noted on physical examination. Complete blood count revealed severe leukocytosis, severe lymphocytosis, and monocytosis. Splenomegaly, hepatomegaly, and lymph node enlargement were detected on radiographic and ultrasonographic examination. Immunophenotyping was performed using peripheral blood mononuclear cells (PBMCs). The majority of lymphocytes exhibited the following profiles: CD3 − CD79a − (97.5%), CD4 − CD8 − (98.6%), CD21 − CD79a − (98.4%), CD34 − (0.1%), CD45 + (99.6%), major histocompatibility complex class II + (99.5%), and CD14 − (0.5%). Based on the immunophenotyping results, possible differentials considered included the following: the majority of lymphocytes may be natural killer (NK) cell clones, plasma cell clones, or show aberrant expression or loss of CD21 marker due to the neoplastic nature of the cells. Further flow cytometry was performed using antibodies against CD3, CD5, CD94, and granzyme B. The combined results indicated that the predominant lymphocyte subset in the PBMCs was CD3 − CD5 − CD21 − CD94 − granzyme B − . To confirm monoclonality and exclude the aberrant loss of CD markers, a polymerase chain reaction for antigen receptor rearrangement (PARR) assay was conducted. The PARR assay, using DNA from blood and lymph node samples, showed B-cell monoclonality. Immunocytochemistry using PBMCs showed that the plasma cell marker Multiple Myeloma Oncogene 1 (MUM1) was not expressed. Therefore, the diagnosis was confirmed to be B-cell CLL. Conclusion Immunophenotyping can help subclassify the type of lymphoid leukemia; however, as tumor cells can show aberrant expression or loss of the CD21 marker, combining immunophenotyping with the PARR assay could yield a more accurate diagnosis.

CLLU1, a disease-specific gene associated with chronic lymphoid leukemia (CLL), is located on chromosome 12q22. Previous studies considered CLLU1 to be a non-coding RNA; however, recent research has discovered that its coding sequence region possesses the potential to encode a short peptide similar to interleukin-4. Remarkably, abnormally elevated expression of CLLU1 has only been detected in chronic lymphoid leukemia among all hematological cancers. High CLLU1 expression often indicates more malignant pathological features and an unfavorable prognosis for patients. Importantly, the expression level of CLLU1 remains unaffected by the passage of time or therapeutic interventions, thus rendering it a novel prognostic marker. This article provides a comprehensive summary of relevant research findings on CLLU1 in the context of CLL prognosis and clinical applications, aiming to guide subsequent theoretical and clinical investigations in this field.

Background: Chronic lymphoid leukemia (CLL) is one of the most prevalent types of leukemia, which is responsible for a remarkable mortality rate in the world. This study aimed to investigate the global trend of this cancer from 1990 to 2015 and to determine the relationship between trend of CLL mortality rate and Human Development Index (HDI) throughout the world. Methods: The age-standardized mortality rate data of all countries of the world (per 100,000) were extracted from the GBD database. In addition, the HDI values for the studied countries in different years were obtained from the UNDP database. The statistical analysis was performed using the mixed-effects location-scale model in the SAS software, version 9.4. Results: The findings of the statistical modeling showed a downward slope for CLL Age Standardized Mortality Rate (ASMR) for total world countries ( ). We also find a significant association between CLL ASMR and HDI. Countries with higher HDI had higher level of CLL ASMR in years 1990 to 2015 with a negative slope. Furthermore, countries with lower HDI had Lower level of CLL ASMR with rather fixed rates in this period. Conclusion: These findings showed a decreasing trend of global CLL ASMR in the previous decades, although, the fixed trend of CLL ASMR in countries with low HDI is worrisome. The health policymakers should make more efforts to decrease the mortality due to this cancer in these countries.

Pathomorphological study of trephinobiopsy specimens from 129 patients with lymphoproliferative and myeloproliferative diseases was carried out over the course of chemotherapy. Combinations of initial and manifest myelofibrosis (loose network of reticulin fibers and extensive network of reticulin and collagen fibers, respectively) predominated at the debut of chronic myeloid leukemia, chronic lymphoid leukemia, and multiple myeloma. Manifest myelofibrosis was detected in patients with chronic myeloid leukemia without hematological response (failure of normalization of hematological values) and in patients with progressing and relapsing multiple myeloma. Combinations of foci of initial and manifest myelofibrosis were most incident in patients with progressing and relapsing chronic lymphoid leukemia. The incidence of myelofibrosis was higher in patients with multiple myeloma and chronic lymphoid leukemia progression and relapses and in patients with chronic myeloid leukemia without hematological response than at the disease debut and in case of response to chemotherapy. The response to chemotherapy in patients with chronic myeloid leukemia and chronic lymphoid leukemia was associated with a decrease in the incidence of myelofibrosis. In patients with multiple myeloma responding to chemotherapy, the incidence of myelofibrosis did not change in comparison with the disease debut.

Background: Richter syndrome (RS) represents a major unmet need in the lymphoma field, being refractory to chemoimmunotherapy and targeted agents. The BCL-2 inhibitor venetoclax in combination with dose-adjusted EPOCH-R chemoimmunotherapy showed promising efficacy in patients affected by RS. However, responses were not durable, suggesting the need for further treatment optimization. Methods: Here, we report two cases of RS achieving long-term complete remission with intensified chemoimmunotherapy (Rituximab-G-MALL B-ALL/NHL2002 regimen) plus venetoclax induction, followed by haploidentical hematopoietic stem cell transplant (allo-HSCT). Venetoclax was given continuously for 14 consecutive days after every Rituximab-G-MALL cycle in off-label use. An accelerated venetoclax rump-up schedule was used in both patients to reach the maximal dose. Maximal venetoclax dose was 300 mg and 400 mg in patient 1 and patient 2, respectively. Results: The combined treatment was well tolerated, with no major infective complications or non-hematological toxicities. In both patients, immunosuppression was discontinued within day 180 after transplant with no graft-versus-host-disease flares. Both patients are alive and in continuous complete remission after 60 and 72 months following allo-HSCT. Conclusions: This report supports the feasibility of a combination treatment with BCL-2 inhibitors and intensive chemoimmunotherapy as a bridge to allo-HSCT in RS.