Lymphocytic Leukemia Research Articles

Advances in Bruton tyrosine kinase (Btk) inhibition are steered by Bruton tyrosine kinase phylogeny.

Bruton tyrosine kinase (Btk) has long been known to play a key role in chronic lymphatic leukaemia, Waldenström macroglobulinaemia and other B-cell proliferative disorders. An impressive programme of drug discovery and clinical development led to the approval of covalent and non-covalent Btk inhibitors that became pillars of treatment of such malignancies. However, both a risk of cardiovascular events and the emergence of an elusive mutational landscape seem to complicate the clinical use of each Btk inhibitor. In this plain language mini-review, we show that the search for better Btk inhibitors is challenged by the ancestral origin of Btk, its homology with innocent kinases in cardiovascular system and unique phylogenetic-like modalities with which Btk can mutate upon exposure to one inhibitor or another. Whereas basic and clinical pharmacology is already at work to explore new avenues of Btk inhibition, phylogeny remains behind the curtain to steer achievements and failures in this field.

Pediatric Cancer Epidemiology for 2021–2023 Based on the Cancer Registry of Indonesia’s National Referral Hospital

Objective: This study aimed to present epidemiological data on pediatric cancers based on the hospital-based cancer registry (HBCR) at Indonesia’s National Referral Hospital. Material and Methods: This descriptive study analyzed data on pediatric cancers from the HBCR for 2021–2023. Demographical data, including age, gender, diagnosis, and admission year, were extracted from the HBCR data. Univariate data analysis was conducted. Results: This study included 344 patients, consisting of 202 males and 142 females. Of those patients, 92 (26.7%) were admitted in 2021, 142 (41.3%) in 2022, and 110 (32%) in 2023. The highest cancer incidence was observed in patients aged 2–5 years (34.9%) and the lowest in those aged <2 years (11.9%). The three most common reported cancers were lymphoid leukemia (47.4%), myeloid leukemia (11.6%), and retinoblastoma (9.6%). Conclusion: Males predominated over females due to the substantial prevalence of leukemia cases. Most pediatric cancers were observed in those aged 2–5 years. While the distributions of cancer varied by age and gender, leukemia remained the leading pediatric cancer.

Intraoperative Frozen Section Biopsy for the Auxiliary Diagnosis of Transmural Intestinal Intermediate T-Cell Canine Lymphoma

Intestinal lymphoma is characterized by a malignant lymphoid neoplasm with multifactorial causes, variable clinical symptoms, and, in some cases, rapid progression. This article describes a case of intestinal lymphoma in a dog that had a history of diarrhea lasting two months, accompanied by episodes of hematochezia, which was treated using the CHOP 19 protocol. A seven-year-old male Golden Retriever presented to a veterinary clinic with clinical signs of diarrhea, prostration, and the presence of bloody feces, as reported by the owner. Initial examinations, including hematology, serum biochemistry, and imaging, revealed an abnormal structure in the intestinal region. Considering the circumstances, a surgical procedure was conducted with the aid of a trans-surgical frozen section biopsy. This biopsy aimed to verify the presence of the neoplasm, assess the suspected diagnosis, evaluate the viability of the surgical margins, and determine the possibility of expanding the surgical area. An enterectomy with enteroanastomosis and trans-surgical biopsy was performed, leading to an initial diagnosis of intestinal lymphoma. The tissue fragment was sent for immunohistochemistry, which ultimately confirmed the diagnosis of intestinal T-cell lymphoma. The patient underwent the CHOP protocol for 19 weeks, but during the maintenance phase, abdominal ultrasound examination findings indicated tumor recurrence. Despite being informed of the potential benefits of further chemotherapy, the owner opted not to continue treatment for the animal. Frozen section biopsy can help with diagnosis during surgery, avoiding more invasive procedures and the removal of lymph nodes, since in some cases, the systemic treatment of the disease is recommended.

Integrative analysis disclosing UQCRC1 as a potential prognostic and immunological biomarker of lung adenocarcinoma.

Lung cancer is one of the most malignant cancers in the world. Approximately 40 % of lung cancer cases are lung adenocarcinoma (LUAD). Exploring new biomarkers was an urgent need for treatments of LUAD. Here, we aimed to perform a pan-cancer analysis of ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) and verify it in LUAD. Compared to normal samples, we observed that UQCRC1 was significantly enhanced in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), LUAD, liver hepatocellular carcinoma (LIHC), and several other cancers. In terms of overall survival, UQCRC1 was positively associated with poor prognosis of LUAD and skin cutaneous melanoma (SKCM). Almost more than 8 % deeply deleted frequency of UQCRC1 was showed in lymphoid neoplasm diffuse large B-cell lymphoma (DLBC). In LUAD, SKCM, and a few cancers, UQCRC1 was negatively correlated with the infiltration of B cells and cancer-associated fibroblasts. As regards further mechanism analysis, we found that UQCRC1 modulated cancer progression via mitochondrial related metabolism and oxidative phosphorylation. Taking advantage of the Kras-driven spontaneous LUAD mice model, online single-cell data, and clinical tissues, we particularly confirmed that UQCRC1 was highly expressed in LUAD and acted as a prognostic marker for LUAD. These findings implied that UQCRC1 played an important role in cancers, especially in LUAD.

Associations Between Immune-Related Conditions and Lymphoid Disorders: An Analysis of the Diverse All of Us Research Program

Introduction: Studies on the association between immune-mediated disorders and lymphoid disorders have been very limited, especially in diverse populations. The objective of this study is to evaluate the relationship between a variety of immune diseases and lymphoid malignancies. Methods: The NIH “All of Us” database was utilized to perform a cross-sectional analysis between lymphoid disorders and various immune diseases. The adjusted multivariable logistic regression analysis was performed in R to examine the association between lymphoid disorders such as leukemia, lymphoma, and plasma cell neoplasms against a variety of autoimmune diseases. Results: In the study cohort of 316,044 patients, we found significant associations between lymphomas and the aforementioned immune-mediated diseases, with the exception of dermatomyositis and scleroderma. Lymphoid leukemias showed significant associations (p < 0.001) with several autoimmune conditions, including psoriasis, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, and hyperthyroidism. In plasma cell neoplasms, significant associations were found in all but dermatomyositis, scleroderma, vitiligo, and atopic dermatitis (p < 0.001). Conclusions: In this population-level analysis, the majority of immune-mediated diseases were found to be significantly correlated with an increased incidence of lymphoid malignancies. As such, patients diagnosed with immune-mediated diseases should undergo close surveillance and early screening with the goal of early identification and treatment of lymphoid malignancies.

Antigen receptor ITAMs provide tonic signaling by acting as guanine nucleotide exchange factors to directly activate R-RAS2.

The small GTPase R-RAS2 regulates homeostatic proliferation and survival of T and B lymphocytes and, when present in high amounts, drives the development of B cell chronic lymphocytic leukemia. In normal and leukemic lymphocytes, R-RAS2 constitutively binds to antigen receptors through their immunoreceptor tyrosine-based activation motifs (ITAMs) and promotes tonic activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Here, we examined the molecular mechanisms underlying this direct interaction and its consequences for R-RAS2 activity. R-RAS2 exhibited direct, high-affinity interactions with ITAM peptides derived from B and T cell receptors through a proline-rich sequence in the hypervariable domain of R-RAS2. In resting T and B cells, the presence of antigen receptors at the plasma membrane was sufficient to promote the activation of R-RAS2 and PI3K, and mutations that abolished the interaction of R-RAS2 with ITAMs reduced R-RAS2 signaling. Binding to ITAMs increased GDP-GTP exchange on R-RAS2 through a mechanism distinct from that by which conventional cytosolic guanosine nucleotide exchange factors (GEFs) activate RAS proteins. These results define antigen receptors as noncanonical GEFs involved in the basal activation state of R-RAS2 in lymphocytes. Such a mechanism may underlie the leukemic transformation of B cells that occurs when wild-type R-RAS2 is present in high amounts.

Cutaneous involvement in multiple myeloma. A rare entity.

Cutaneous involvement in multiple myeloma is rare and may present as nodules mimicking other lymphoid neoplasms. It typically occurs late in the course of the disease and is associated with an aggressive clinical course and poor prognosis.

A Hiding Lymphoma: Angioimmunoblastic T Cell Lymphoma — A Case Report

Angioimmunoblastic T-cell lymphoma (AITL) is now a well-established subtype of mature peripheral T-cell lymphoma (PTCL). Advanced-stage disease is common with uncharacteristic laboratory and autoimmune findings that often slow or mask the diagnosis. AITL afflicts advanced-age individuals with a median age of diagnosis of 65 years of age without a notable gender predisposition. Significant strides in the immunohistochemical and molecular signature of AITL have brought increased ability to diagnose this uncommon type of PTCL. The 2016 World Health Organization classification of lymphoid neoplasms recently acknowledged the complexity of this diagnosis with the addition of other AITL-like subsets. AITL now resides under the umbrella of nodal T-cell lymphomas with follicular T helper phenotype. The treatment of relapsed or refractory AITL remains an unmet need. The spectrum of AITL from diagnosis to treatment is reviewed subsequently in a fashion that may one day lead to personalized treatment approaches in a many-faced disease. Here we report a case of angioimmunoblastic T cell lymphoma which was diagnosed using endoscopic ultrasound guided fine needle biopsy. Our patient’s lab workup was unremarkable and inconclusive, but the correct diagnosis was established using endoscopic ultrasound guided fine needle biopsy. Chemotherapy started after diagnosis and his condition improved.

Long-term side effects of neurotoxicity of antitumor therapy in children who survived lymphoid tumors

Relevance. Improving the diagnosis and treatment of children with lymphoid tumors (LT) contributes to an increase in the number of cured patients. Antitumor therapy has a side effect on the nervous system, and can lead to neurotoxic consequences. Due to the increased life expectancy of children cured of LT, the assessment of the long-term neurotoxic effects of antitumor therapy is relevant.Objective: based on the literature data, to study the long-term neurotoxic side effects of antitumor therapy in children cured of LT.Material and methods. When writing a literature review, data were analyzed in specialized medical databases Pubmed, Scopus, Web of Science on research in children cured of lymphoid tumors from 1993 to 2023.Results. In cured children from lymphoid tumors, the long-term neurotoxic effects of therapy containing methotrexate in high doses are manifested by neurocognitive decline and structural changes in the brain. Late peripheral neuropathy caused by vincristine affects the quality of life of patients in physical and social aspects. However, the prognostic parameters of long-term neurotoxic effects in children cured of LT have not been determined. The issues of monitoring patients in the long term have not been sufficiently studied. This will contribute to the rehabilitation and long-term follow-up of patients with oncohematological diseases, and improve their quality of life.

BCL-2 inhibitors in hematological malignancies: biomarkers that predict response and management strategies.

Apoptosis is an essential characteristic of cancer and its dysregular promotes tumor growth, clonal evolution, and treatment resistance. B-cell lymphoma-2 (BCL-2) protein family members are key to the intrinsic, mitochondrial apoptotic pathway. The inhibition of the BCL-2 family pro-survival proteins, which are frequently overexpressed in B-cell malignancies and pose a fundamental carcinogenic mechanism has been proposed as a promising therapeutic option, with venetoclax (ABT-199) being the first FDA-approved BCL-2 inhibitor. Unfortunately, although BCL-2 inhibition has shown remarkable results in a range of B-cell lymphoid cancers as well as acute myeloid leukemia (AML), the development of resistance significantly reduces response rates in specific tumor subtypes. In this article, we explain the role of BCL-2 family proteins in apoptosis and their mechanism of action that justifies their inhibition as a potential treatment target in B-cell malignancies, including chronic lymphocytic leukemia, multiple myeloma, B-cell lymphomas, but also AML. We further analyze the tumor characteristics that result in the development of intrinsic or inherited resistance to BCL-2 inhibitors. Finally, we focus on the biomarkers that can be used to predict responses to treatment in the name of personalized medicine, with the goal of exploring alternative strategies to overcome resistance.

The Mathematical Model Comparison Between Regular Immunogenic Tumor and Chronic Myelogenous Leukemia (CML)

T cell plays important role in lymphocytic leukemia. And the understanding of T cells would help people to modify the growth of leukemia and administrate the dosage to patients. This paper discussed the use of two different models of ordinary differential equations to analyze leukemia. Although the models may have some differences, both of them focused on analyzing the model to calculate the equilibrium state of the tumor in its absence and presence. Regular Immunogenic tumors use a more basic mathematical model, while the chronic myelogenous leukemia (CML) model adds more complex deformations to it. This study compares the steady states of the models proposed by Kuznetsov et al. and Moore and Li, and incorporates the parameter values used in Moore and Li to compare the disparity between them. The research concluded that there were no significant differences in health trials but there were substantial disparities in disease trials between two models

Evaluation of Complete Blood Count in Chronic Lymphoid Leukemia Patients

Chronic Lymphoid Leukemia (CLL) is characterized by the uncontrolled proliferation of lymphocytes, usually in the elderly, which can lead to various hematological abnormalities in patients. Analysis of hematological parameters is very important for the diagnosis, prognosis, and monitoring of treatment response in CLL. This study aimed to compare the complete blood count (CBC) parameters of CLL patients with a healthy control group. The study included 50 patients diagnosed with CLL and 50 healthy controls without a history of cancer. CBC parameters (WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, RDW-SD, PDW, PLT, MPV, PCT, NEU%, LYM%, MONO%, EOS%, BASO%, NEU#, LYM#, MONO#, EOS#, BASO#, NRBC#) of CLL patients and control group were statistically compared. According to the analysis results, no significant difference was found between MCV, RDW, RDW-SD, PDW, MPV, BASO%, NEU#, and EOS# values of the patient and control groups (p>0.05). However, WBC, RBC, HGB, HCT, LYM%, MONO%, LYM#, MONO#, BASO#, and NRBC# values of the patient group were significantly higher relative to the control group (p<0.05). MCH, MCHC, PLT, PCT, NEU%, and EOS% parameters were significantly higher in the control group relative to the patient group (p<0.05). As a result, significant differences were observed in some CBC parameters between patients and the control groups. Particularly, the significant difference observed in some parameters emphasizes that the hematological profile of CLL can be used in the diagnosis and monitoring processes. Our findings support

Tertiary lymphoid structures and cancer immunotherapy: From bench to bedside.

Tertiary lymphoid structures (TLSs) are organized ectopic lymphoid aggregates within the tumor microenvironment that serve as crucial sites for the development of adaptive antitumor cellular and humoral immunity. TLSs have been consistently documented in numerous cancer types, correlating with improved prognosis and enhanced responses to immunotherapy, especially immune-checkpoint blockade (ICB). Given the potential role of TLSs as predictive biomarkers for the efficacy of ICB in cancer patients, the therapeutic manipulation of TLSs is gaining significant attention as a promising avenue for cancer treatment. Herein, we comprehensively review the composition, definition, and detection methods of TLSs in humans. We also discuss the contributions of TLSs to antitumor immunity, their prognostic value in cancer patients, and their association with therapeutic response to ICB-based immunotherapy. Finally, we present preclinical data supporting the potential of therapeutically manipulating TLSs as a promising approach for innovative cancer immunotherapy.

Is It Time to Assess T Cell Clonality by Next-Generation Sequencing in Mature T Cell Lymphoid Neoplasms? A Scoping Review

Background: T cell clonality is commonly assessed in the diagnostic work-up of mature T cell lymphoid neoplasms. Although fragment-length polymerase chain reaction (FL-PCR) assays are most widely used, next-generation sequencing (NGS) of the TRG and TRB genes is increasingly being used to assess T cell clonality. Objective: The present work is a scoping review of studies that assessed T cell clonality by NGS for diagnostic purposes, including only studies that provided integrated clinicopathologic diagnoses in comparing FL-PCR and NGS assays to evaluate if it is preferable to use NGS-based assays for T cell clonality evaluation in diagnostic pathology. Methods: Papers published from 1992 to 3 August 2024 were searched in PubMed. Twenty-nine cohort studies and five instructive case reports, published from 2013–2024 from the USA, UK, Europe, and Australia that provided integrated clinicopathologic diagnoses and used NGS to evaluate T cell clonality in clinical specimens from patients with mature T cell neoplasms and related non-neoplastic and neoplastic diseases were included, with additional relevant studies. Results: Ten (34.4%) of the 29 cohorts included clinical samples from patients having various cutaneous and non-cutaneous T cell malignancies, related neoplasms, and reactive conditions; 2 (6.8%) studies focused on T cell prolymphocytic leukemia, 16 (55%) on cutaneous T cell lymphoma, and one on pediatric pityriasis lichenoides. Eleven (38%) of the 29 cohort studies compared NGS with FL-PCR assays in 908 clinical samples. Eight (72.7%) of the 11 studies compared TRG FL-PCR with TRG NGS (n = 5), TRB NGS (n = 2), and TRG NGS and TRB NGS (n = 1); the remaining three compared EuroClonality/BIOMED-2 FL-PCR (TRG and TRB) with TRG NGS (n = 1), TRB NGS (n = 1), and the EuroClonality-NGS DNA capture assay (n = 1). TRB NGS was used in 16 (55%) of 29, TRG NGS in 6 (20.6%) of 29, and both TRG and TRB NGS in 7 (24%) of 29. Two (6.8%) of the 29 studies compared TRB NGS with flow cytometric immunophenotyping assays for Vβ and T cell receptor β constant region 1. One additional study compared long-read sequencing with NGS for TRG and TRB rearrangements. Conclusions: NGS is highly specific and sensitive for assessing T cell clonality. NGS precisely tracks unique rearranged sequences, which FL-PCR cannot. NGS findings for clonality must be interpreted in the context of all clinicopathologic and immunophenotypic findings, like FL-PCR. With such interpretations, NGS is much preferable to FL-PCR for evaluating T cell clonality for diagnostic purposes. It is necessary to reduce costs, increase accessibility, and educate providers about NGS for clonality evaluation. TRB NGS has been primarily assessed in the peripheral blood and skin, whereas TRG NGS has also been evaluated in formalin-fixed and non-cutaneous fresh lymphoid tissues. TRG NGS performed better than TRB NGS in comparative studies.

Zn2+ triazamacrocyclic chelators with methylpyridine pendant arms for B-cell apoptosis: a structure-activity study.

Three macrocyclic tacn (1,4,7-triazacyclononane) derivatives containing one, two and three 2-methylpyridine pendant arms (no1py, no2py and no3py), compared to the linear diamine analogue tpen (N,N,N',N'-tetrakis(2-methylpyridinyl)-ethylenediamine) known for its capacity to induce cell apoptosis by Zn2+ chelation and/or ROS production, have shown cytotoxic activity on the Daudi B-cell line and CLL (chronic lymphoid leukemia) primary B cell model. These properties have been evidenced using an Incucyte® Live-Cell Analysis System. Evaluation of caspase 3/7 activation by incubation with the four studied chelators has exhibited caspase-dependent apoptotic death. Investigation of the chelator action mechanism has shown no ROS (reactive oxygen species) production for the macrocyclic chelators no1py, no2py and no3py, unlike the linear counterpart tpen for which ROS production was revealed. A significant inhibition effect of macrocyclic chelator cytotoxicity has been established by extracellular addition of cationic salts (Zn2+ and Cu2+) and the Zinquin emission fluorescence method has evidenced intracellular labile zinc chelation for no2py and no3py, while no1py acts differently. The acid-base properties of the chelators and their Zn2+ complexation constants have been obtained, discussed and correlated with the demonstrated biological properties.

Correlation of Equilibrium Radionuclide Ventriculography Scan with Two-Dimensional Transthoracic Echocardiography for Early Evaluation of the Left Ventricular Ejection Fraction after Anthracycline Treatment in Patients with Acute Lymphoid Leukemia

Introduction: Early diagnosis of cardiac toxicity caused by chemotherapy drugs in acute lymphoid leukemia (ALL) patients can prevent the occurrence of heart failure. Equilibrium radionuclide ventriculography (ERNV) has the advantage of a precise evaluation, while two-dimensional transthoracic echocardiography (2D-TTE) is more widely available. This study aimed to evaluate the correlation of the relevant cardiac toxicity parameters for patients diagnosed with ALL using both of these techniques. Material and methods: Between January 2022 and May 2024, patients with ALL were prospectively evaluated in the hematology department of Imam Khomeini Hospital in Tehran. 2D-TTE and ERNV were performed before and after two cycles of HYPER-CVAD chemotherapy. Patients with cardiac disease, cardiovascular risk or previous anticancer treatment were excluded. Results: Forty-four patients with ALL were included: 24 (54.5%) males and 20 (45.5%) females. The majority of patients (56.8%) were between 20 and 40 years old and had no history of cardiac disease or malignancies. Baseline left ventricular ejection fraction (LVEF) volumes were correlated on 2D-TTE and ERNV (r=0.5; P=0.001). Eleven patients were evaluated after therapy. LVEF values were similar (54.9±8.1 vs. 54.3±4.6; P=0.552) but without a linear correlation (r= 0.3; p=0.409). Only two cardiac parameters were significantly changed after chemotherapy: the pulmonary artery pressure (PAP) on 2D-TTE (24.3±5.5 vs 22.2±5.2; p=0.02) and the time peak filling rate (TTPFR) on ERNV (138.3±39.8 vs 170±52.9 milliseconds; p=0.004). Conclusion: Cardiac function impairment parameters on ERNV and 2D-TTE were similar before and after a cumulative dose of daunorubicin of 100 mg/m2. Before therapy, there was also a linear correlation between values. PAP decreased and TTPFR increased after chemotherapy. Keywords

Revealing the heterogeneity of treatment resistance in less-defined subtype diffuse large B cell lymphoma patients by integrating programmed cell death patterns and liquid biopsy.

Precision medicine in less-defined subtype diffuse large B-cell lymphoma (DLBCL) remains a challenge due to the heterogeneous nature of the disease. Programmed cell death (PCD) pathways are crucial in the advancement of lymphoma and serve as significant prognostic markers for individuals afflicted with lymphoid cancers. To identify robust prognostic biomarkers that can guide personalized management for less-defined subtype DLBCL patients, we integrated multi-omics data derived from 339 standard R-CHOP-treated patients diagnosed with less-defined subtype DLBCL from three independent cohorts. By employing various machine learning algorithms, we pinpointed eight pivotal genes linked to PCD, specifically FLT3, SORL1, CD8A, BCL2L1, COL13A1, MPG, DYRK2 and CAMK2B. Following this, we established a Programmed Cell Death Index (PCDI) utilizing the aforementioned genes and amalgamated it with pertinent clinical characteristics to formulate a predictive nomogram model for prognosis. We observed a significant correlation between the PCDI, pre-treatment circulating tumour DNA (ctDNA) burden, minimal residual disease (MRD) status and immune features. Furthermore, our research indicated that patients with elevated PCDI scores could potentially show resistance to conventional chemotherapy treatments, yet they might derive an advantage from alternative inhibitors targeting specific signalling pathways. Conclusively, leveraging these results, we have created an online analytical tool (https://xulymphoma.shinyapps.io/PCDI_pred/) designed for the prognostic prediction of patients with less-defined subtype DLBCL. This tool facilitates the forecasting of outcomes for these patients, enhancing the precision of their clinical management. KEY POINTS: Developing the Programmed Cell Death Index (PCDI) utilizing multiple machine learning algorithms for patients with less-defined subtype diffuse large B-cell lymphoma. The difference in clinical characteristics, circulating tumour DNA burden and immune profiling between patients with distinct PCDI groups. A potentially effective regimen was speculated for patients with high PCDI scores who tend to exhibit worse progression-free survival.

HemaCisDB: An Interactive Database for Analyzing Cis-Regulatory Elements Across Hematopoietic Malignancies.

Noncoding cis-regulatory elements (CREs), such as transcriptional enhancers, are key regulators of gene expression programs. Accessible chromatin and H3K27ac are well-recognized markers for CREs associated with their biological function. Deregulation of CREs is commonly found in hematopoietic malignancies yet the extent to which CRE dysfunction contributes to pathophysiology remains incompletely understood. Here, we developed HemaCisDB, an interactive, comprehensive, and centralized online resource for CRE characterization across hematopoietic malignancies, serving as a useful resource for investigating the pathological roles of CREs in blood disorders. Currently, we collected 922 ATAC-seq, 190 DNase-seq, and 531 H3K27ac ChIP-seq datasets from patient samples and cell lines across different myeloid and lymphoid neoplasms. HemaCisDB provides comprehensive quality control metrics to assess ATAC-seq, DNase-seq, and H3K27ac ChIP-seq data quality. The analytic modules in HemaCisDB include transcription factor (TF) footprinting inference, super-enhancer identification, and core transcriptional regulatory circuitry analysis. Moreover, HemaCisDB also enables the study of TF binding dynamics by comparing TF footprints across different disease types or conditions via web-based interactive analysis. Together, HemaCisDB provides an interactive platform for CRE characterization to facilitate mechanistic studies of transcriptional regulation in hematopoietic malignancies. HemaCisDB is available at https://hemacisdb.chinablood.com.cn/.

Lymphoproliferative tumors in rheumatic diseases

The development of lymphoid tumors in patients with rheumatic diseases can significantly worsen the quality of life and negatively affect the prognosis. The article presents modern data on the relationship between lymphoid tumors and rheumatic diseases. Practical differential diagnosis guidelines of T cell large granular lymphocytic leukemia in patients with rheumatoid arthritis and Felty’s syndrome are given. The results of the study of pathogenesis and bio‑ logical predictors of diffuse large B cell lymphoma in patients with rheumatic diseases are presented. This study of the lymphoproliferative tumor pathogenesis in patients with rheumatic diseases sheds light on the mechanisms underlying the development of sporadic lymphoproliferative tumors and autoimmune diseases, as well as on the pro‑ gress in the treatment of these diseases.

Dynamic susceptibility contrast perfusion MRI helps in differentiating double-expressor from non-double-expressor subtypes in primary central nervous system lymphoma.

In the 2016 WHO Classification of Lymphoid Tissue Neoplasms, co-expression of MYC and BCL2 is newly designated as double expressor lymphoma. Patients with primary central nervous system lymphoma with double expressor (DE-PCNSL) have been reported to have a higher risk of recurrence and a worse prognosis than those with PCNSL without double expressor (non-DE-PCNSL). The aim of this study was to determine whether DE-PCNSL has characteristic clinical and MR imaging features compared to non-DE-PCNSL. This study included 36 immunocompetent patients with PCNSL, including 16 with double expressor and 20 without double expressor. The enhancement pattern and the values of apparent diffusion coefficient (ADC), relative cerebral blood volume (rCBV), leakage-corrected rCBV, and K2 at enhancing lesions were compared between the DE-PCNSL and non-DE-PCNSL groups. The mean and minimum values from the ROI on ADC maps were designated as ADCmean and ADCmin, respectively. The data of rCBV, leakage-corrected rCBV and K2 were obtained from dynamic susceptibility contrast (DSC) perfusion MRI. The Kaplan-Meier method was used to estimate progression-free survival (PFS) differences. DE-PCNSL was significantly more common in women (12 of 16 patients, 75%) compared to non-DE-PCNSL (7 of 20 patients, 35%; P =.02). The rCBV ratio and leakage-corrected rCBV ratio were significantly lower in DE-PCNSL compared to non-DE-PCNSL (P =.02 and P =.03, respectively). There was no significant difference in the enhancement pattern and ADCmean, ADCmin and K2 values between the two groups. DE-PCNSL tended to have a shorter PFS than non-DE-PCNSL, although the difference was not significant. rCBV and leakage-corrected rCBV may help differentiate double-expressor from non-double-expressor subtypes in PCNSL.