Chronic Lymphatic Leukemia Research Articles

Causal role of genetically predicted 731 immune cell phenotypes in chronic lymphatic leukemia: a bidirectional Mendelian randomization study

Causal role of genetically predicted 731 immune cell phenotypes in chronic lymphatic leukemia: a bidirectional Mendelian randomization study

Diagnosis of canine B-cell chronic lymphoid leukemia with a CD21 negative phenotype using the LT21 clone CD21 antibody in flow cytometry: a case report

BackgroundChronic 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 presentationA 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.ConclusionImmunophenotyping 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.

Causal relationship between beta-2 microglobulin and B-cell malignancies: genome-wide meta-analysis and a bidirectional two-sample Mendelian randomization study.

Beta-2 microglobulin (β2M) is acknowledged as a prognostic biomarker for B-cell malignancies. However, insights into the impact of β2M on B-cell malignancy risk, and vice versa, are limited. We conducted a genome-wide meta-analysis (GWMA), bidirectional two-sample Mendelian randomization (TSMR) analysis, and pathway enrichment analysis to explore the causal relationship between β2M and B-cell malignancies and the underlying biological processes. The GWMA identified 55 lead SNPs across five genomic regions (three novel: WDR72, UMOD, and NLRC5) associated with β2M. In the UKB, genetically predicted β2M showed a positive association with diffuse large B-cell lymphoma (DLBCL; odds ratio [OR]: 1.742 per standard deviation increase in β2M; 95% confidence interval [CI]: 1.215-2.498; P = 3.00 × 10-3; FDR = 7.50× 10-3) and Hodgkin lymphoma (HL; OR: 2.270; 95% CI: 1.525-3.380; P = 5.15 × 10-5; FDR =2.58 × 10-4). However, no associations were found with follicular lymphoma (FL), chronic lymphoid leukemia (CLL), or multiple myeloma (MM). Reverse TSMR analysis revealed no association between genetically predicted B-cell malignancies and β2M. In FinnGen, β2M was found to be associated with an increased risk of DLBCL (OR: 2.098; 95% CI: 1.358-3.242; P = 8.28 × 10-4; FDR = 4.14 × 10-3), HL (OR: 1.581; 95% CI: 1.167-2.142; P = 3.13 × 10-3; FDR = 5.22 × 10-3), and FL (OR: 2.113; 95% CI: 1.292-3.455; P = 2.90 × 10-3; FDR = 5.22 × 10-3). However, no association was found with CLL or MM. Reverse TSMR analysis indicated that genetically predicted DLBCL, FL, and MM may perturb β2M levels. Pathway enrichment analysis suggested that the innate immune system represents a convergent biological process underlying β2M, DLBCL, and HL. Our findings suggested that elevated levels of β2M were associated with an increased risk of DLBCL and HL, which is potentially linked to dysfunction of the innate immune system.

A prospective, longitudinal study of health-related quality of life and contributing factors and its impact on medication adherence to oral anticancer agents in real-world patients with leukemia.

270 Background: Suboptimal rates of non-adherence have been reported in leukemia patients taking oral anticancer agents (OAAs), largely attributed to treatment-related symptoms (TRS). This survey was conducted to describe the complex relationship between adherence, TRS, and health-related quality of life (HRQOL). Methods: This is a single arm, observational, prospective, longitudinal study. Patients with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphoid leukemia (CLL) on OAAs completed a telephone survey, which included Wilson’s 3-item medication adherence measure, the PROMIS 10-item Global Health Scale (domains: overall QOL, physical/mental/social health), and assessment of TRS using PRO-CTCAE. This survey was repeated three times, two to three months apart. Optimal adherence was defined as greater than 90% per Wilson’s measure. Spearman’s correlation, chi-square tests, as appropriate, to evaluate the association between medication adherence and HRQOL. Results: 77 patients completed the first survey, of which 60.3% were male, with an average age of 62 years old. Diagnoses were: CML (n=28), CLL (n=19), AML (n=19), and ALL (n=11). Optimal adherence rates declined from 70.2% in the 1 st survey to 55% by the 3 rd survey, whereas HRQOL measures remained stable over time. Most patients (92.2%, n= 71) reported at least one TRS with 42.25% (n= 30) reporting ≥6 symptoms. Patients without TRS were more likely to be adherent than those with symptoms (100% vs. 67%, p=0.17). Specifically, patients with no pain were associated with higher adherence (p= 0.084). Those who rated their mental health and overall quality of life (QOL) as ‘excellent,’ ‘very good,’ or ‘good’ had numerically a higher adherence rate (73% with optimal adherence) than those rating it as ‘fair’ or ‘poor,’ (59-61% had optimal adherence), although not statistically significant. The number of TRS reported from PRO-CTCAE significantly affected patients’ reported QOL: patients reporting 0-5 number of TRS were more likely to report higher QOL (‘excellent,’ ‘very good,’ or ‘good’) than those reporting ≥6 TRS (p = 0.0004). Conclusions: Adherence rates in leukemia patients on OAAs were suboptimal and declined over time. TRS were common and inversely associated with HRQOL, even though adherence was not strongly correlated: patients with high adherence still reported fair or poor HRQOL. Given the numerous and varied factors contributing to non-adherence and HRQOL issues in leukemia patients, a multi-modality support program is essential.

Current ideas on the pathogenesis of osteoporosis in chronic lymphatic leukemia (literature review)

Background. Chronic lymphocytic leukemia (CLL) is the second most common hematological malignancy without a trend towards a decrease in its incidence. 66 % of patients with CLL experience bone fractures as a result of osteoporosis in all age groups, and the detection frequency is no more than 15 %. Insufficient understanding of the osteoporosis pathogenesis in CLL leads to problems in diagnosis, prevention and therapy.The aim of the study. To analyze modern data on the features of the osteoporosis pathogenesis in chronic lymphocytic leukemia.Results and discussion. Osteoporosis is formed when osteoresorption prevails over osteosynthesis due to intercellular interactions of bone tissue and the immune system, dysregulation of intracellular signaling pathways RANKL/RANK/OPG, Wnt, FoxO, RUNX2, initiated by cytokines, growth factors, prostaglandins, and hormones. The degree of osteoresorption in CLL is associated with the severity of the clinical course, chemotherapy and hormonal deprivation. The osteoporosis pathogenesis in CLL is considered as part of a complex set of events, including, firstly, the interaction between leukemic cells (overexpression of PTHrP, RANKL) and bone cells (synthesis of growth factors), which forms a vicious circle of osteoresorption and tumor growth. Secondly, pro-inflammatory markers in CLL (tumor necrosis factor α, interleukin (IL) 1β, IL-6, IL-8, IL-11, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, transforming growth factor β, prostaglandin E2) limit osteoblast-induced osteosynthesis and stimulate the expansion of osteoclasts from monocytic suppressor cells of myeloid origin with or without the participation of the RANKL/RANK system. Thirdly, oxidative stress in CLL and impaired efficiency of antioxidant protection with the participation of fibroblast growth factor 23, transcription factor Nrf-2 with activation of JNK, ERK1/2, NF-κB, and also an increase in the RANKL/OPG ratio lead to inhibition of osteoblastogenesis.Conclusion. Analyzing and systematizing data on the osteoporosis pathogenesis in CLL are instrumental for the development of diagnostic criteria for osteoporosis in chronic lymphocytic leukemia that are much-needed in clinical practice and for the improvement of therapeutic tactics.

Investigation of erythrocyte membrane lipid profile, oxidative stress and dna damage parameters in patients with chronic lymphoid leukemia

Purpose: Chronic lymphocytic leukemia (CLL) is the most seen type of leukemia in adults. There are few biomarkes that are used for better understanding how oxidative stress is involved in the pathophysiology of hematologic malignency.We aimed to oxidative stress, DNA damage and erythrocyte membrane lipid profile in CLL patients in this study. The study is included 38 CLL patients and 38 age-sex matched controls. Materials and method: Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), DNA damage examination with Comet assay, serum 8-OHdG measurement and gas chromatographic analysis were performed between the case and control groups. Results: It was observed that TOS and OSI values were higher in the case group than in the control group (p=0.014 and p=0.022, respectively). DNA damage measured by Comet method was found to be increased in the case group (p0.05). Conclusion: It has been shown that CLL patients had higher oxidant capasity as consequence. Oxidative stress and DNA damage are increased in CLL patients in this study. It is early to evaulate on erythrocyte membrane lipid profile in CLL patients. However, the study can be ligthed the way future studies on the subject.

Assessment of the Efficacy and Safety of Acalabrutinib in Chronic Lymphocytic Leukemia (CLL): A Systematic Review and Meta‑Analysis .

Chronic lymphoid leukemia (CLL) is a common adult leukemia that has been treated with chemoimmunotherapy, which has significant toxicity among patients. Advances in CLL understanding have led to targeted therapies, such as Bruton's tyrosine kinase (BTK) inhibitors. Acalabrutinib is one of the second-generation BTK inhibitors and offers improved selectivity, reducing off-target effects. This systematic review and meta-analysis analyze data from multiple clinical trials to assess acalabrutinib efficacy and safety among patients with CLL. A literature search was carried out in PubMed, Cochrane Controlled Register of Trials (CENTRAL), MEDLINE (Medical Literature Analysis and Retrieval System Online), and Ovid databases for articles published until 2024. The outcomes included the overall response rate (ORR), complete response rate(CRR), 24-month progression-free survival rate, and grade ≥3 adverse events (AEs). Meta-analysis was performed using jamovi software. The search strategy yielded 823 records. After assessing the eligibility of the retrieved studies, the systematic review finally included six clinical trials, including 808 patients. The findings demonstrated significant efficacy of acalabrutinib, with a pooled ORR (P < 0.001) and a pooled CRR (P = 0.001). The pooled 24-month progression-free survival (PFS) rate showed a significant improvement in maintaining patient safety and treatment effectiveness (P <0.001). However, hematological AEs such as neutropenia, anemia, and thrombocytopenia were reported across studies. The pooled grade ≥ 3 AEs rate was 0.51 (95% CI: 0.21-0.81, I² = 98.21%, P <0.001), indicating a notable incidence of severe side effects. Acalabrutinib is an active drug in treating CLL that induces significant clinical benefits concerning response rates and PFS. However, acalabrutinib should be managed carefully to mitigate the risk of severe AEs. Further trials should be focused on assessing and modulating the safety of acalabrutinib.

Circular RNA as a Biomarker for Diagnosis, Prognosis and Therapeutic Target in Acute and Chronic Lymphoid Leukemia.

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.

Incidence and Risk Factors for Arterial Thrombosis in Patients with Acute Leukemia and Lymphoid Malignancies: A Retrospective Single-Center Study.

The treatment of patients with hematological malignancies and acute arterial thrombosis (ATE) is challenging due to the risk of bleeding complications during treatment. Data on the incidence and risk factors for ATE in this group are very limited. We aimed to evaluate the incidence and risk factors for ATE in patients with acute leukemia (AL) and lymphoid malignancies. Patients with acute leukemia (AL), lymphoid malignancies, and ATE diagnosed following cancer diagnosis, who were treated and followed at the Department of Hematology, Karolinska University Hospital, 2005-2020, were candidates for inclusion in this study. Retrospective data on malignancy, ATE, and risk factors were collected. No differences in either the 15-year incidence of ATE (1.4%) nor in the risk factors for cardiovascular disease (CVD) between patients with AL and lymphoid malignancies and ATE were found. ATE at diagnosis was more frequent in patients with AL and lymphoid malignancies (excluding chronic lymphatic leukemia, CLL). Patients with AL and lymphoid malignancies have a similar risk of ATE when compared to each other and the general population, regardless of platelet levels. No difference could be found in the presence of CVD risk factors between patients with AL and lymphoid malignancies presenting with ATE.

Challenges in addressing Chronic Lymphoid Leukemia: when to treat or not to treat?

A leucemia linfoide crônica (LLC) é uma neoplasia maligna caracterizada pela proliferação clonal de linfócitos morfologicamente maduros, mas imuno-incompetentes, que se acumulam em medula óssea, sangue periférico, baço e linfonodos, onde ocorrepredominantemente a expansão clonal de células B CD5+ e CD23+. A mutação cromossômica mais comum é del (13q), estando as mutações de TP53 associadas a um pior prognóstico. A LLC acomete pacientes de meia-idade e idosos, sendo frequentemente encontrada nos países ocidentais, eos pacientes do sexo masculino são mais acometidos do que os de sexo feminino. A maioria dos indivíduos são diagnosticados incidentalmente durante um hemograma de rotina, uma vez que a doença apresenta grande heterogeneidade nas manifestações clínicas. Os critérios para iniciar o tratamento baseiam-se nos sistemas de estadiamento Rai e Binet e na presença de sintomas relacionados à doença.Este estudo objetiva apresentar uma análise abrangente sobre a leucemia linfoide crônica e o desafio de quando iniciar ou não o tratamento. Para tal, foi realizada uma revisão bibliográfica com busca por artigos científicos e meios eletrônicos publicados entre 2015 e 2022.

Knocking Out CD70 Rescues CD70-Specific NanoCAR T Cells from Antigen-Induced Exhaustion.

CD70 is an attractive target for chimeric antigen receptor (CAR) T-cell therapy for the treatment of both solid and liquid malignancies. However, the functionality of CD70-specific CAR T cells is modest. We optimized a CD70-specific VHH-based CAR (nanoCAR). We evaluated the nanoCARs in clinically relevant models in vitro, using co-cultures of CD70-specific nanoCAR T cells with malignant rhabdoid tumor organoids, and in vivo, using a diffuse large B-cell lymphoma patient-derived xenograft (PDX) model. Although the nanoCAR T cells were highly efficient in organoid co-cultures, they showed only modest efficacy in the PDX model. We determined that fratricide was not causing this loss in efficacy but rather CD70 interaction in cis with the nanoCAR-induced exhaustion. Knocking out CD70 in nanoCAR T cells using CRISPR/Cas9 resulted in dramatically enhanced functionality in the diffuse large B-cell lymphoma PDX model. Through single-cell transcriptomics, we obtained evidence that CD70 knockout CD70-specific nanoCAR T cells were protected from antigen-induced exhaustion. In addition, we demonstrated that wild-type CD70-specific nanoCAR T cells already exhibited signs of exhaustion shortly after production. Their gene signature strongly overlapped with gene signatures of exhausted CAR T cells. Conversely, the gene signature of knockout CD70-specific nanoCAR T cells overlapped with the gene signature of CAR T-cell infusion products leading to complete responses in chronic lymphatic leukemia patients. Our data show that CARs targeting endogenous T-cell antigens negatively affect CAR T-cell functionality by inducing an exhausted state, which can be overcome by knocking out the specific target.

Efficacy of catheter ablation in patients with persistent atrial fibrillation on chronic ibrutinib therapy

Abstract Background Ibrutinib represents a cornerstone in the management of B-Cells malignancies and chronic lymphatic leukaemia. This drug however was associated with a 5-fold increased risk of developing atrial fibrillation (AF). The consequences of AF in this category of frailty patients such as heart failure may lead to the need of Ibrutinib withdrawal, which is considered a disease modifying therapy. Purpose This study aims to evaluate the safety and efficacy of catheter ablation in managing AF in patients on chronic ibrutinib therapy. Methods this study evaluated 20 consecutive patients from two centres in Italy who developed persistent AF during chronic therapy with Ibrutinib for chronic lymphatic leukaemia or small lymphocytic lymphoma and underwent AF catheter ablation from 2016 to 2020. Antiarrhythmic drugs were withdrawn because of side effects and drug interaction. All receive pulmonary vein (PV) isolation + isolation of left atrial posterior wall (PW) and superior vena cava. A standardized protocol was performed to confirm persistent PVI and elicit any triggers originating from non-PV sites. Ablation of non-PV sites triggering runs of atrial tachyarrhythmias was left to operator's discretion. Exclusion criteria were age&amp;lt;18 years and history of AF before ibrutinib therapy. Patients were monitored for arrhythmia at quarterly office visits, ECGs, 7-day Holter monitoring and event recorders during the first year followed by biannual checkups during the remaining part of the follow-up period. Results 12 patients received PV+PW+SVC isolation plus ablation of non-PV trigger (Group 1) whereas 8 receive only PV+PW+SVC isolation (Group 2). 10 (83,3%) patients in group 1 remained arrhythmia-free without the need for additional antiarrhythmic drugs while only 3 (37,5%) in group 2 maintained sinus rhythms. Non pulmonary triggers were mostly found in left atrial appendage (5/12, 41,6%), coronary sinus (4/12, 33,3%) and crista terminalis (3/12 25%). More than one trigger was found in 4 (33.3) patients. After 22.3 ±3.6 months follow-up, patients with ablation of induced non-PV triggers had a significantly higher arrhythmia control than those whose triggers were not ablated (Chi – square p value: 0.035; Log rank p value: 0.014) (Fig.1). 5 patient that received left atrial appendage isolation underwent a left atrial appendage closure with Watchman device 3 months after atrial fibrillation ablation. Conclusion Catheter ablation in this category of patients seems to be a safe and effective tool for managing atrial fibrillation in patients with persistent AF on chronic ibrutinib therapy; an ablation strategy that includes as a first line therapy non pulmonary vein triggers appears to be an effective approach when compared to pulmonary vein plus posterior wall only. This approach will allow continuation of ibrutinib treatment, which markedly enhances the prognosis and diminishes the risk of adverse cardiovascular events in this patient population.Kaplan-Meier curve showing recurrence-fr

Copper-doped titanium dioxide nanoparticles decorated on 2D-hexagonal boron nitride nanosheets for susceptible electrochemical detection of an anti-cancer drug in environmental and biological samples.

Chlorambucil (CML) cures chronic lymphatic leukemia (white blood cell cancer). A high dose of CML can cause several side effects like bone marrow suppression, anemia, peripheral neuropathy, and infertility in the human body. In this research, we have synthesized a nanocomposite based on copper-doped titanium dioxide (CuTiO2) adorned with 2D hexagonal boron nitride (CuTiO2@BN) for the efficient electrochemical detection of CML. A series of characterization techniques FT-IR, XRD, Raman spectroscopy, SEM, TEM, EDAX XPS, and electrochemical characterization were used to analyze the CuTiO2@BN nanocomposite structural and morphological compositions. The sensing performance of the CuTiO2@BN modified GCE for CML detection has been assessed using voltammetry methods. The chronoamperometry technique analyzed the kinetics of the electrochemical oxidation of CML at CuTiO2@BN/GCE. The CuTiO2@BN-based glassy carbon electrode (GCE) has a synergetic electro-catalytic effect on CML oxidation due to its many active sites, enhanced surface area, fast charge transfer, and numerous defects. For the detection of CML, the suggested electrochemical sensor exhibits excellent selectivity, low limit of detection (LOD) as found 5.0nM, wide linear ranges (0.02-8000µM), and quick reaction times.

Generation of iPSC derived CD19 CAR iNK cells for treatment of autoimmune disorders

Abstract Treatment of autoimmune diseases (ADs) relies on broad immunosuppressive agents that are often not curative. Autologous CAR T cell approaches demonstrated disease remission in patients with Systemic lupus erythematosus (SLE). Among cellular abnormalities typical for ADs, NK cells dysfunction was reported. We believe that using iPSC derived CD19 CAR NK cells (iNK cells) to eliminate disease-causing circulating plasma cells could be a novel therapeutic approach for ADs mediated by B cells. Evotec’s validated GMP iPSC line was genetically modified by a knock-in of a CD19-CAR and differentiated into iNK cells using a feeder-free 3D differentiation process. Successful knock-in was confirmed by flow cytometry. Expression of the CAR did not negatively impact the differentiation of the iNK cells. The CD19 CAR iNK cell phenotype and scRNA sequencing profiles are comparable to blood-derived NK cells. To evaluate the ability of CD19 CAR iNK cells to selectively eliminate primary B cells, patient-derived B cell chronic lymphatic leukemia (CLL) cells and primary B cells from healthy donors were co-cultured with CAR iNK cells. Compared to wildtype (WT) iNK cells, CD19 CAR iNK showed specific killing of CD19-positive CLL cells and primary B cells. iPSC-derived CD19-CAR NK cells show increased cytotoxicity and specific targeting of CD19 positive primary patient and healthy subject derived B cells, demonstrating their potential suitability for the treatment of ADs such as SLE.

Covalent docking-driven virtual screening of extensive small-molecule libraries against Bruton tyrosine kinase for the identification of highly selective and potent novel therapeutic candidates

Bruton tyrosine kinases (BTKs) play critical roles in various diseases, including chronic lymphatic leukemia (CLL), Waldenström Macroglobulinemia, Marginal Zone Lymphoma, Mantle Cell Lymphoma (MCL), and Graft Versus Host diseases. BTKs are a family of tyrosine kinases involved in B lymphocyte signal transduction, development, and maturation. Their overexpression can lead to cancer as they are essential for the activation of the B Cell Receptor (BCR) signaling pathway. Blocking the activation of BTKs presents a promising approach for treating CLL. This study was centered around the identification of small-molecule therapeutics that have an impact on human BTK. The covalently bound Ibrutinib molecule, recognized for its ability to inhibit BTK, was used as the query molecule. IUPAC text files containing molecular fragments of Ibrutinib were employed to virtually screen five different libraries comprising small-molecules, resulting in the screening of over 2.4 million synthesized compounds. Covalent docking simulations were applied to the selected small-molecules obtained through text mining from databases. Potent hit molecules capable of inhibiting BTKs through virtual screening algorithms were identified, paving the way for novel therapeutic strategies in the treatment of CLL.

Biological Therapy for Psoriasis in Cancer Patients: An 8-Year Retrospective Real-Life Study.

Background: It is now recognized that psoriasis plays a key role in the development of several comorbidities, such as cardiovascular disease, and metabolic syndrome. Some authors have hypothesized that patients with psoriasis may have an increased risk of developing certain types of cancer. The efficacy and safety of biologic drugs are well-documented in clinical trials and in real-life studies. However, there is limited evidence on the safety of the use of biologic treatments in cancer patients with psoriasis, and the use of this therapeutic class in patients with a pre-existing or concomitant malignancy is still debated. Methods: We have conducted a retrospective observational study of a group of oncology patients with moderate-to-severe psoriasis treated with biologic therapy at the Dermatology Clinic of the University of Naples Federico II, during the period from 2016 to 2024. We included 20 adult patients; in 15 of them the diagnosis of neoplasm preceded the start of treatment biologic, while four of these patients had been diagnosed with cancer during the course of therapy biologics. Results: The most represented neoplasms in our population were breast carcinoma, prostate carcinoma, thyroid carcinoma, and chronic lymphatic leukemia. Anti-IL17 drugs were the most frequently prescribed (47.7%), followed by anti-IL23p19 (36.8%), anti-IL-12/23 (10.5%) and anti-TNF alpha (5.26%). All patients showed improvement of psoriasis after starting the therapy. Conclusions: Our experience supports the effectiveness and safety of biological therapy for psoriasis in patients with a history of cancer or recent onset neoplasia.

CLLU1 as an emerging biomarker in chronic lymphoid leukemia.

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.

A Rare Case of Hairy Cell Leukemia with COVID Infection: A Case Report

Abstract Hairy cell leukemia (HCL) is a distinct subset of chronic lymphoid leukemia, presents with unique features, including the characteristic "hairy" projections seen in neoplastic B cells. We reported a case on hairy cell leukemia (HCL), emphasizing the challenges posed by this rare hematological malignancy, especially in the context of concurrent health crises such as the COVID-19 pandemic. This malignancy, though uncommon, necessitates comprehensive diagnostic methodologies, such as peripheral blood studies, flow cytometry, and bone marrow biopsy. Treatment strategies for HCL involve tailored approaches based on symptomatic presentations. Purine analogs, cladribine and pentostatin, stand as first-line interventions, showcasing efficacy in inducing and sustaining remission. However, the prolonged immunosuppression resulting from these treatments warrants vigilant monitoring for potential infectious complications. Emerging therapies, such as the BRAF inhibitor vemurafenib, provide additional options for refractory or progressive cases. The post-treatment phase demands meticulous follow-up, with an emphasis on regular blood work assessments by an oncology nurse and primary care physician. Our case further highlights the need for heightened awareness among healthcare professionals, particularly in the post-COVID-19 phase, where persistent symptoms led to the discovery of an underlying hematological disorder. Keywords: Hairy cell leukemia, Evan syndrome, Covid-19.

Determination of Some miRNA Expression Levels in Chronic Lymphoid Leukemia Patients

Chronic lymphoid leukemia (CLL) is a type of cancer that occurs as a result of the accumulation of morphologically small, mature-looking lymphocytes. CLL is the most common type of leukemia in Western countries, where it accounts for 30% of all leukemias. Accounts for only 10% of all leukemias in Asian populations. MicroRNAs (miRNAs) are non-protein-coding single-stranded RNA molecules approximately 18-25 nucleotides long, forming a class of endogenous small RNAs. Research has shown that microRNAs can function as oncogenes or tumor suppressors in CLL. Although the expression levels of microRNA 133a and microRNA 452 have been determined in many cancers, including lung, prostate and colon cancer, expression levels in CLL patients have not been determined. Therefore, in our study, the expression levels of miRNA 133a and miRNA 452 in CLL patients will be calculated quantitatively using the Real-Time PCR method. As for the method steps, in the first stage, whole blood samples will be taken. miRNA will be isolated from the whole blood samples taken, cDNA will be synthesized from the miRNA samples, and finally, expression levels will be determined with the Real-Time PCR method using miRNA 133a, miRNA452 specific primers and U6 primer as the reference gene. The data obtained will be analyzed and interpreted with the SPSS package program. This study will be conducted to determine whether these two miRNAs can guide early diagnosis and diagnosis in CLL patients and to provide preliminary information to clinicians and contribute to the literature on this subject.

ZAP-70 augments tonic B-cell receptor and CCR7 signaling in IGHV–unmutated chronic lymphocytic leukemia

AbstractExpression of ZAP-70 in a subset of patients with chronic lymphocytic leukemia (CLL) positively correlates with the absence of immunoglobulin heavy-chain gene (IGHV) mutations and is indicative of a more active disease and shorter treatment-free survival. We recently demonstrated that ZAP-70 regulates the constitutive expression of CCL3 and CCL4, activation of AKT, and expression of MYC in the absence of an overt B-cell receptor (BCR) signal, bona fide functions of BCR activation. We, here, provide evidence that these features relate to the presence of a constitutive tonic BCR signal, exclusively found in IGHV-unmutated CLL and dependent on the ZAP-70–mediated activation of AKT and its downstream target GSK-3β. These findings are associated with increased steady-state activation of CD19 and SRC. Notably this tonic BCR signal is not present in IGHV-mutated CLL cells, discordantly expressing ZAP-70. Results of quantitative mass spectrometry and phosphoprotein analyses indicate that this ZAP-70–dependent, tonic BCR signal regulates CLL cell migration through phosphorylation of LCP1 on serine-5. Indeed, we show that CCL19- and CCL21-induced chemotaxis is regulated by and dependent on the expression of ZAP-70 through its function to enhance CCR7 signaling to LCP1. Thus, our data demonstrate that ZAP-70 converges a tonic BCR signal, exclusively present in IGHV-unmutated CLL and CCR7-mediated chemotaxis.