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Frontiers in Oncology 2024
PubMed: 38756664
DOI: 10.3389/fonc.2024.1412843 -
Cancer Medicine May 2024Recent studies have found a high prevalence of hepatitis B virus (HBV) infection in patients with non-Hodgkin's lymphoma (NHL), especially B-cell non-Hodgkin's lymphoma...
OBJECTIVE
Recent studies have found a high prevalence of hepatitis B virus (HBV) infection in patients with non-Hodgkin's lymphoma (NHL), especially B-cell non-Hodgkin's lymphoma (B-NHL). However, most studies did not classify it and analyze the correlation between HBV and its various subtypes.
METHODS
The authors retrospectively analyzed 1424 patients with lymphoma. Differences in the prevalence of HBV infection in patients with different pathological types of lymphoma were analyzed. The clinical characteristics, progression-free survival (PFS), and overall survival (OS) of HBV-positive and negative B-NHL subtypes were compared according to HBV infection.
RESULTS
The HBV infection rate in NHL patients was 7.65%, which was higher than that in HL patients (2.59%, p < 0.05). The HBV infection rate in the B-NHL was higher than that in the T-cell non-Hodgkin's lymphoma (T-NHL) (8.14% vs. 4.95%). The HBV infection rate in the aggressive B-NHL was similar to that of the indolent B-NHL (8.30% vs. 7.88%), and the highest HBV infection rates were found in diffuse large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, but no significant differences in clinical characteristics, PFS, and OS were seen between HBV-positive and negative patients in the two subtypes.
CONCLUSIONS
There was an association between HBV infection and the development of NHL and HBV infection may play a role in the pathogenesis of B-NHL, but not T-NHL.
Topics: Humans; Retrospective Studies; Male; Female; Middle Aged; Hepatitis B; Adult; Aged; Hepatitis B virus; Young Adult; Prevalence; Lymphoma, Non-Hodgkin; Adolescent; Aged, 80 and over; Lymphoma, B-Cell; Progression-Free Survival
PubMed: 38752442
DOI: 10.1002/cam4.7284 -
Technology in Cancer Research &... 2024Small nucleolar RNAs (snoRNAs) form clusters within the genome, representing a mysterious category of small non-coding RNAs. Research has demonstrated that aberrant... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Small nucleolar RNAs (snoRNAs) form clusters within the genome, representing a mysterious category of small non-coding RNAs. Research has demonstrated that aberrant snoRNAs can contribute to the development of various types of cancers. Recent studies have identified snoRNAs as potentially valuable biomarkers for the diagnosis or/and prognosis of cancers. However, there has been a lack of comprehensive reviews on prognostic and diagnostic snoRNAs across different types of cancers.
METHODS
We conducted a systematic search of various databases including Google Scholar, Medline, Cochrane, Scopus, PubMed, Embase, ScienceDirect, Ovid-Medline, Chinese National Knowledge Infrastructure, WanFang, and SinoMed with a time frame reception to December 30, 2022. A total of 49 relevant articles were included in our analysis, consisting of 21 articles focusing on diagnostic aspects and 41 articles focusing on prognostic aspects. Pooled odds ratio, 95% confidence intervals (CIs), and hazard ratio (HR) were utilized to evaluate clinical parameters and overall survival (OS), respectively.
RESULT
The findings indicated that area under the curve, sensitivity, and specificity were 0.85, 75%, and 80% in cancer, respectively. There was a possibility that snoRNAs had a positive impact on the diagnosis (risk ratio, RR = 2.95, 95% CI: 2.75-3.16, = 0.000) and OS (HR = 1) in cancer. Additionally, abnormally expressed snoRNAs were associated with a positive impact on OS time for chronic lymphocytic leukemia (HR: 0.88, 95%Cl: 0.69-1.11, < 0.00001), colon adenocarcinoma (HR: 0.97, 95%Cl: 0.91-1.03, < 0.0001), and ovarian cancer (HR: 0.98, 95%Cl: 0.98-0.99, < 0.00001). However, dysregulated snoRNAs of colon cancer and colorectal cancer had a negative impact on OS time (HR = 3.01 and 1.01 respectively, < 0.0001).
CONCLUSION
The results strongly suggested that snoRNAs could serve as potential novel indicators for prognosis and diagnosis in cancers. This systematic review followed the guidelines of the Transparent Reporting of Systematic Review and Meta-Analyses (PROSPERO register: CRD42020209096).
Topics: Humans; RNA, Small Nucleolar; Biomarkers, Tumor; Prognosis; Neoplasms; ROC Curve
PubMed: 38752263
DOI: 10.1177/15330338241245939 -
JPMA. the Journal of the Pakistan... Apr 2024To assess the association of serum protein electrophoresis abnormalities with clinicopathological characteristics, and its impact on overall survival in chronic...
OBJECTIVE
To assess the association of serum protein electrophoresis abnormalities with clinicopathological characteristics, and its impact on overall survival in chronic lymphocytic leukaemia patients.
METHODS
The prospective study was conducted at Haematology and Immunology departments of the University of Health Sciences, Lahore, Pakistan, from 2019 to 2022, and comprised newly diagnosed chronic lymphocytic leukaemia patients. Lactate dehydrogenase and beta-2 microglobulin levels were measured by spectrophotometric principle, whereas serum protein electrophoresis was determined through commercially available capillary electrophoresis systems. Patients were followed up for 2 years post-diagnosis. Data was analysed using SPSS 21.
RESULTS
Of the 50 patients, 40(80%) were males and 10(20%) were females. The overall mean age was 60±11 years. Serum protein electrophoresis was available for 40(80%) patients, and, among them, 12(30%) patients had abnormal levels, while 29(72.5%) required treatment. Overall response rate was 25(86.2%), and median two-year overall survival was 16.5 months (95% confidence interval: 10-20 months). Abnormal serum protein electrophoresis was significantly associated with Binet stage C, lower mean haemoglobin levels and higher median levels of lactate dehydrogenase and beta-2 microglobulin (p<0.05)). Regarding overall survival, the survival curves of chronic lymphocytic leukaemia patients with normal and abnormal serum protein electrophoresis status differed significantly (p=0.04).
CONCLUSION
Abnormal serum protein electrophoresis could be considered a surrogate marker for advanced chronic lymphocytic leukaemia disease.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Female; Male; Middle Aged; Prognosis; Aged; Prospective Studies; beta 2-Microglobulin; Blood Protein Electrophoresis; L-Lactate Dehydrogenase; Pakistan; Hemoglobins; Survival Rate; Neoplasm Staging; Blood Proteins
PubMed: 38751267
DOI: 10.47391/JPMA.10116 -
Journal of Clinical and Experimental... May 2024The increasing number of treatment options for patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in Japan...
The increasing number of treatment options for patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in Japan underscores the critical need to comprehend their treatment preferences. In this study, individual semi-structured interviews with 20 Japanese patients with diagnosis of MCL or CLL/SLL were conducted and qualitatively analyzed to elicit concepts important for patients regarding treatment selection. Although effectiveness and safety were imperative for treatment selection, convenience and quality of life were also reported as important attributes. Over the course of their disease journey, patients reported diverse and changing preferences in terms of treatment characteristics. Additionally, there was a discrepancy between their desired and actual levels of involvement in shared decision-making with physicians about treatment choices. Optimal personalized care for better outcomes of patients with MCL and CLL/SLL hinges on healthcare professionals acknowledging individual patient needs and preferences within their cultural, societal and personal context.
PubMed: 38749721
DOI: 10.3960/jslrt.24016 -
Protein Science : a Publication of the... Jun 2024AF9 (MLLT3) and its paralog ENL(MLLT1) are members of the YEATS family of proteins with important role in transcriptional and epigenetic regulatory complexes. These...
AF9 (MLLT3) and its paralog ENL(MLLT1) are members of the YEATS family of proteins with important role in transcriptional and epigenetic regulatory complexes. These proteins are two common MLL fusion partners in MLL-rearranged leukemias. The oncofusion proteins MLL-AF9/ENL recruit multiple binding partners, including the histone methyltransferase DOT1L, leading to aberrant transcriptional activation and enhancing the expression of a characteristic set of genes that drive leukemogenesis. The interaction between AF9 and DOT1L is mediated by an intrinsically disordered C-terminal ANC1 homology domain (AHD) in AF9, which undergoes folding upon binding of DOT1L and other partner proteins. We have recently reported peptidomimetics that disrupt the recruitment of DOT1L by AF9 and ENL, providing a proof-of-concept for targeting AHD and assessing its druggability. Intrinsically disordered proteins, such as AF9 AHD, are difficult to study and characterize experimentally on a structural level. In this study, we present a successful protein engineering strategy to facilitate structural investigation of the intrinsically disordered AF9 AHD domain in complex with peptidomimetic inhibitors by using maltose binding protein (MBP) as a crystallization chaperone connected with linkers of varying flexibility and length. The strategic incorporation of disulfide bonds provided diffraction-quality crystals of the two disulfide-bridged MBP-AF9 AHD fusion proteins in complex with the peptidomimetics. These successfully determined first series of 2.1-2.6 Å crystal complex structures provide high-resolution insights into the interactions between AHD and its inhibitors, shedding light on the role of AHD in recruiting various binding partner proteins. We show that the overall complex structures closely resemble the reported NMR structure of AF9 AHD/DOT1L with notable difference in the conformation of the β-hairpin region, stabilized through conserved hydrogen bonds network. These first series of AF9 AHD/peptidomimetics complex structures are providing insights of the protein-inhibitor interactions and will facilitate further development of novel inhibitors targeting the AF9/ENL AHD domain.
Topics: Peptidomimetics; Humans; Intrinsically Disordered Proteins; Histone-Lysine N-Methyltransferase; Models, Molecular; Oncogene Proteins, Fusion; Crystallography, X-Ray; Protein Domains; Myeloid-Lymphoid Leukemia Protein
PubMed: 38747396
DOI: 10.1002/pro.5019 -
Frontiers in Immunology 2024Chimeric antigen receptor T cells (CAR T) targeting CD7 for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) showed promising efficacy and safety in some...
Chimeric antigen receptor T cells (CAR T) targeting CD7 for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) showed promising efficacy and safety in some clinical trials. However, most of them were bridged with allogeneic hematopoietic stem cell transplantation (allo-HSCT). We described successful treatment with preventive donor-derived anti-CD7 CAR-T therapy in a case of refractory T lymphoblastic lymphoma following allo-HSCT, who could not receive autologous anti-CD7 CAR-T products due to the low-quality of T lymphocytes. To date, the patient's complete remission has persisted for 20 months after HSCT.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Transplantation, Homologous; Immunotherapy, Adoptive; Antigens, CD7; Receptors, Chimeric Antigen; Male; Tissue Donors; T-Lymphocytes; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome; Adult
PubMed: 38745670
DOI: 10.3389/fimmu.2024.1381308 -
BMC Cancer May 2024In chronic lymphocytic leukaemia (CLL), comorbidities assessed by the CLL comorbidity index (CLL-CI) have been associated with outcomes in Western cohorts. We conducted...
In chronic lymphocytic leukaemia (CLL), comorbidities assessed by the CLL comorbidity index (CLL-CI) have been associated with outcomes in Western cohorts. We conducted a retrospective analysis of an unselected Middle Eastern cohort of newly diagnosed CLL patients seen at the Kuwait Cancer Control Center (n = 300). Compared to Western studies, these Middle Eastern patients were diagnosed at a younger age (median of 59) and had a higher comorbidity burden (69% non-low risk CLL-CI). A higher CLL-CI score was independently associated with significantly shorter event-free survival and greater risk of death. Our analysis demonstrates that CLL-CI is a valuable tool for comorbidity assessment and prognostic influence in (relatively young) Middle Eastern CLL patients.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Female; Male; Middle Aged; Comorbidity; Prognosis; Retrospective Studies; Aged; Adult; Kuwait; Aged, 80 and over; Age Factors
PubMed: 38741031
DOI: 10.1186/s12885-024-12343-1 -
Annals of Medicine Dec 2024Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an... (Meta-Analysis)
Meta-Analysis
Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis.
BACKGROUND
Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events. This study assessed the efficacy and safety of CAR T-cell therapy for r/r B-ALL.
METHODS
The literature search was performed on four databases. Efficacy parameters included minimal residual disease negative complete remission (MRD-CR) and relapse rate (RR). Safety parameters constituted cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
RESULTS
Anti-CD22 showed superior efficacy with the highest MRD-CR event rate and lowest RR, compared to anti-CD19. Combining CAR T-cell therapy with haploidentical stem cell transplantation improved RR. Safety-wise, bispecific anti-CD19/22 had the lowest CRS rate, and anti-CD22 showed the fewest ICANS. Analysis of the costimulatory receptors showed that adding CD28ζ to anti-CD19 CAR T-cell demonstrated superior efficacy in reducing relapses with favorable safety profiles.
CONCLUSION
Choosing a more efficacious and safer CAR T-cell treatment is crucial for improving overall survival in acute leukaemia. Beyond the promising anti-CD22 CAR T-cell, exploring costimulatory domains and new CD targets could enhance treatment effectiveness for r/r B-ALL.
Topics: Humans; Immunotherapy, Adoptive; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Antigens, CD19; Sialic Acid Binding Ig-like Lectin 2; Receptors, Chimeric Antigen; Child; Treatment Outcome; Neoplasm, Residual; Cytokine Release Syndrome; Recurrence; Neurotoxicity Syndromes
PubMed: 38738799
DOI: 10.1080/07853890.2024.2349796 -
Cureus Apr 2024is a Gram-negative bacillus commonly seen in immunocompromised individuals and often misdiagnosed as . is an opportunistic pathogen found in aquatic environments. It...
is a Gram-negative bacillus commonly seen in immunocompromised individuals and often misdiagnosed as . is an opportunistic pathogen found in aquatic environments. It is a nonfatal infection that has low virulence and endorses susceptibility to many common antibiotics. We report a case of a 53-year-old immunocompromised male who was managed for bacteremia.
PubMed: 38738051
DOI: 10.7759/cureus.57965