Myeloid Leukemia Research Articles

The Correlation Between Motivation and Self-Care Mangement Among Leukemia Patients Based on Orem's Theory

Introduction: Leukemia is one of the most diagnosed types of cancer and a cause of death worldwide. Patients who experience severe side effects of cancer treatment tend to experience less than optimal self-care management. Leukimia patients in treatment often complain of fatigue, weakness, lack of energy, and nausea which hinder them in self-care management. The purpose of this study was to determine the relationship between motivation and self-care management. Methods: This study used an analytic descriptive research design with a cross sectional approach. Population on this research were members of Chronic Granulocytic Leukemia (it is known as “ELGEKA”), East Java, Indonesia. The sample size was 69 respondents using purposive sampling. The independent variable was motivation and the dependent variable was self-care management. Data was analyzed using Spearman Rho analysis with level of significance 0.05. Results: The results of this study indicated that there was a relationship between motivation and self-care management (p=0.000) and (r=0,531). Discussion: Motivation has a significant relationship with self-care management in leukemia patients based on Orem's theory. The higher the motivation, the higher self-care management. Good self-care management involves nutrition and fluid management, physical activity, stress management, complementary therapy, information and support seeking, and medication adherence. Conclusion: Nurses have an important role in identifying and increasing patient motivation to carry out self-care management and changing their attitudes to improve health and disease care. The recommendation for future researchers is to develop research with interventions to improve self-care management in leukemia patients.

Metformin mitigates doxorubicin-induced cardiotoxicity via the AMPK pathway

To explore whether metformin reduces cardiotoxicity of doxorubicin through the AMPK pathway. We analyzed the data of 123 patients with myeloid leukemia, non-Hodgkin's lymphoma, or breast cancer receiving doxorubicin for phased chemotherapy, including 43 patients receiving combined treatment with metformin (test group) and 80 without metformin treatment (control group). The changes in plasma levels of CK-MB, LDH, and BNP, left ventricular ejection fraction (EF) and left ventricular fractional shortening (FS) of the patients were observed. The effect of treatments with metformin and doxorubicin, alone or in combination, on myocardial damage, cardiac function and myocardial cell apoptosis were also observed in C57BL/6 mice with AMPKα2 gene knockout (AKO). CK-MB, LDH and BNP levels increased and EF and FS decreased significantly in the control group after chemotherapy (P<0.05). In the test group, CK-MB, LDH and BNP levels were significantly lowered after the combined treatment (P<0.05), while EF and FS did not undergo obvious changes (P>0.05). CK-MB, LDH and BNP levels were lower and EF and FS were higher significantly in the test group than in the control group after the treatment (P<0.05). Doxorubicin treatment reduced FS in both wild-type and AKO mice, but the reduction was less obvious in AKO group (P<0.05). The combined treatment restored FS in wild-type mice (P<0.05) but not in AKO mice. Doxorubicin significantly increased LDH and cTnI levels in both wild-type and AKO mice, but with smaller increments in the latter (P<0.05); The combined treatment with metformin reduced doxorubicin-induced elevation of LDH and cTnI levels in the wild-type mice (P<0.05) but not in AKO group (P>0.05). Doxorubicin increased myocardial cell apoptosis in both mice (P<0.01) but less strongly in AKO mice (P<0.05). Chemotherapy with doxorubicin causes cardiotoxicity, which can be mitigated by combined treatment with metformin possibly through a mechanism involving the AMPK pathway.

Omicron related COVID-19 prevention and treatment measures for patients with hematological malignancy and strategies for modifying hematologic treatment regimes

The Omicron variant of SARS-CoV-2 has rapidly become the dominant strain worldwide due to its high transmissibility, although it appears to be less pathogenic than previous strains. However, individuals with hematological malignancy (HM) and COVID-19 remain susceptible to severe infection and mortality, especially those with chronic lymphocytic leukemia (CLL) and those undergoing chimeric antigen receptor T-cell (CAR-T) treatment. Hematologists should thoroughly assess the severity of the patient’s hematological disease and the potential risk of SARS-CoV-2 infection before initiating chemotherapy or immunosuppressive treatment. Vaccination and booster doses are strongly recommended and patients with a poor vaccine response may benefit from long-acting COVID-19 neutralizing monoclonal antibodies (such as Evusheld). Early use of small molecule antiviral drugs is recommended for managing mild COVID-19 in HM patients and those with severe immunodeficiency may benefit from SARS-CoV-2 neutralizing monoclonal antibody therapy and high-titer COVID-19 convalescent plasma (CCP). For moderate to severe cases, low-dose glucocorticoids in combination with early antiviral treatment can be administered, with cytokine receptor antagonists or JAK inhibitors added if the condition persists or worsens. In the treatment of hematological malignancies, delaying chemotherapy is preferable for CLL, acute leukemia (AL), and low-risk myelodysplastic syndrome (MDS), but if the disease progresses, appropriate adjustments in dosage and frequency of treatment are required, with the avoidance of anti-CD20 monoclonal antibody, CAR-T and hematopoietic stem cell transplantation (HSCT). Patients with chronic myelocytic leukemia (CML) and myeloproliferative neoplasms (MPNs) can continue current treatment. What’s more, non-drug protective measures, the development of new vaccines and antiviral drugs, and monitoring of mutations in immunocompromised populations are particularly important.

Taches de Roth et infiltrations périvasculaires révélant une leucémie myéloïde chronique

Taches de Roth et infiltrations périvasculaires révélant une leucémie myéloïde chronique

Cordycepin from Cordyceps militaris ameliorates diabetic nephropathy via the miR-193b-5p/MCL-1 axis

BackgroundDiabetic nephropathy (DN) is a chronic kidney disease that develops in patients with diabetes mellitus. Cordycepin (CRD), a secondary metabolite produced by Cordyceps militaris, has a variety of bioactive properties. In this study, DN mice and high glucose (HG)-treated HK-2 were used to evaluate the diagnostic value of CRD.MethodsQuantitative real-time PCR (qRT-PCR), western blotting, immunofluorescence analysis, and immunohistochemical staining were used to assess changes in mRNA and protein expression. Oxidative stress was evaluated by detecting the production of reactive oxygen species (ROS) and the activity of antioxidant enzymes. Cell apoptosis was detected by the TUNEL and flow cytometric methods. The interaction of miR-193b-5p and myeloid leukemia 1 (MCL-1) was examined by bioinformatics analysis and luciferase reporter assay. The protective effects of CRD on DN mice were evaluated by examining DN related biochemical indicators and renal histopathology.ResultsIn response to HG, the level of miR-193b-5p was elevated, whilst the level of MCL-1 was downregulated, and CRD therapy reversed this behavior. MCL-1 was further identified to be miR-193b-5p target. CRD attenuated HG-induced cell damage, inflammation and abnormal energy metabolism. Mechanistic investigations on in vitro models confirmed that protective effect of CRD against HG challenge to HK-2 cells is mediated through the regulation of expression of miR-193b-5p/MCL-1 axis. By examining DN related biochemical markers and renal histopathology, the protective effects of CRD on DN mice was assessed.ConclusionsIn summary, CRD decreased oxidative stress and inflammation by increasing miR-193b-5p and inactivating downstream MCL-1 in DN, hinting the pivotal values of CRD and miR-193b-5p in the management of DN.

Altered expression of imprinted genes in patients with cytogenetically normal‑acute myeloid leukemia: Implications for leukemogenesis and survival outcomes.

Genomic imprinting, an epigenetic mechanism that regulates gene expression from parental chromosomes, holds substantial relevance in multiple cancers, including hematopoietic malignancies. In the present study, the expression of a panel of 16 human imprinted genes in bone marrow samples from 64 patients newly diagnosed with cytogenetically normal-acute myeloid leukemia (CN-AML) were examined alongside peripheral blood samples from 85 healthy subjects. The validated findings of the present study revealed significant upregulation of seven genes [COPI coat complex subunit gamma 2 (COPG2), H19 imprinted maternally expressed transcript (H19), insulin like growth factor 2 (IGF2), PEG3 antisense RNA 1 (PEG3-AS1), DNA primase subunit 2 (PRIM2), solute carrier family 22 member 3 SLC22A3 and Zinc finger protein 215 (ZNF215)] in patients with CN-AML (P<0.001). Notably, the expression level of H19 exhibited an inverse association with the survival duration of the patients (P=0.018), establishing it as a predictive marker for two- and five-year survival in patients with CN-AML. Kaplan-Meier analysis demonstrated that patients with lower H19 expression had superior two- and five-year survival rates compared with those with higher H19 expression. The results of the present study highlighted the association between loss of imprinting and leukemogenesis in CN-AML, underscoring the significance of H19 imprinting loss as a prognostic indicator for unfavorable two- and five-year survival in CN-AML patients.

Isolation of anticancer bioactive secondary metabolites from the sponge-derived endophytic fungi Penicillium sp. and in-silico computational docking approach.

Fungus-derived secondary metabolites are fascinating with biomedical potential and chemical diversity. Mining endophytic fungi for drug candidates is an ongoing process in the field of drug discovery and medicinal chemistry. Endophytic fungal symbionts from terrestrial plants, marine flora, and fauna tend to produce interesting types of secondary metabolites with biomedical importance of anticancer, antiviral, and anti-tuberculosis properties. An organic ethyl acetate extract of Penicillium verruculosum sponge-derived endophytic fungi from Spongia officinalis yielded seven different secondary metabolites which are purified through HPLC. The isolated compounds are of averufin (1), aspergilol-A (2), sulochrin (3), monomethyl sulochrin (4), methyl emodin (5), citreorosein (6), and diorcinol (7). All the seven isolated compounds were characterized by high-resolution NMR spectral studies. All isolated compounds', such as anticancer, antimicrobial, anti-tuberculosis, and antiviral, were subjected to bioactivity screening. Out of seven tested compounds, compound (1) exhibits strong anticancer activity toward myeloid leukemia. HL60 cell lines have an IC50 concentration of 1.00μm, which is nearly significant to that of the standard anticancer drug taxol. A virtual computational molecular docking approach of averufin with HL60 antigens revealed that averufin binds strongly with the protein target alpha, beta-tubulin (1JFF), with a -10.98 binding score. Consecutive OSIRIS and Lipinski ADME pharmacokinetic validation of averufin with HL60 antigens revealed that averufin has good pharmacokinetic properties such as drug score, solubility, and mutagenic nature. Furthermore, aspergilol-A (2) is the first report on the Penicillium verruculosum fungal strain. We concluded that averufin (1) isolated from Penicillium verruculosum can be taken for further preliminary clinical trials like animal model in-vivo studies and pharmacodynamic studies. A future prospect of in-vivo anticancer screening of averufin can be validated through the present experimental findings.

2041P The prevalence of hematologic adverse events (HAEs) and myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) in patients (pts) with advanced high grade ovarian carcinoma (aHGOC) receiving PARP inhibitor (PARPi), with or without a germline BRCA pathogenic variant

2041P The prevalence of hematologic adverse events (HAEs) and myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) in patients (pts) with advanced high grade ovarian carcinoma (aHGOC) receiving PARP inhibitor (PARPi), with or without a germline BRCA pathogenic variant

EVI1-mediated Programming of Normal and Malignant Hematopoiesis.

Ecotropic viral integration site 1 (EVI1), encoded at the MECOM locus, is an oncogenic zinc finger transcription factor with diverse roles in normal and malignant cells, most extensively studied in the context of hematopoiesis. EVI1 interacts with other transcription factors in a context-dependent manner and regulates transcription and chromatin remodeling, thereby influencing the proliferation, differentiation, and survival of cells. Interestingly, it can act both as a transcriptional activator as well as a transcriptional repressor. EVI1 is expressed, and fulfills important functions, during the development of different tissues, including the nervous system and hematopoiesis, demonstrating a rigid spatial and temporal expression pattern. However, EVI1 is regularly overexpressed in a variety of cancer entities, including epithelial cancers such as ovarian and pancreatic cancer, as well as in hematologic malignancies like myeloid leukemias. Importantly, EVI1 overexpression is generally associated with a very poor clinical outcome and therapy-resistance. Thus, EVI1 is an interesting candidate to study to improve the prognosis and treatment of high-risk patients with "EVI1high" hematopoietic malignancies.

Acute and chronic kidney injury during therapy for pediatric acute leukemia: A report from the Leukemia Electronic Abstraction of Records Network (LEARN).

Children with acute leukemia are at increased risk of kidney injury. Using electronic health record data from three centers between 2010 and 2018, this study retrospectively described acute kidney injury (AKI) and chronic kidney disease (CKD) prevalence in children with acute lymphoblastic or myeloid leukemia (ALL, AML) using Common Terminology Criteria for Adverse Events (CTCAE) and Kidney Disease Improving Global Outcomes (KDIGO) definitions. AKI during therapy was 25% (ALL) and 32% (AML) using CTCAE, versus 84% (ALL) and 74% (AML) using KDIGO. CKD prevalence was low and Grade 1/Stage 2. Further investigation is needed to optimally define kidney injury in acute leukemia.

Therapeutic potential of single-nucleotide polymorphism-mediated interleukin-6 receptor blockade in cancer treatment: A Mendelian randomization study

BackgroundInterleukin-6 (IL-6) is a crucial member of the cytokine network and plays a pivotal role in the pathogenesis of various diseases, including cancer. IL-6 receptor (IL-6R) blockade is widely employed as a therapeutic strategy; however, its efficacy in anticancer therapy remains ambiguous. MethodsAn inverse variance-weighted Mendelian randomization (MR) analysis was conducted to assess the causal effects exerted by IL-6R blockade in remediating cancer. Drug-targeted single-nucleotide polymorphisms (SNPs) were introduced within 300 kb of the IL-6R gene. An instrumental variable comprising 26 SNPs represented IL-6 signaling downregulation and C-reactive protein level reduction. Datasets pertaining to the 33 types of cancer investigated in this study were acquired from the FinnGen genome-wide association study. ResultsThe selected instrumental variable lowered fibrinogen levels, confirming its ability to mimic IL-6R blockade. IL-6R blockade exhibited therapeutic effects on five different cancer types documented in the FinnGen database (N = 334,364, including 76,781 cancer patients): bladder (odds ratios (OR) = 0.563), laryngeal (OR = 0.293), eye (OR = 0.098), gallbladder (OR = 0.059), and myeloid leukemia (OR = 0.442); however, it simultaneously elevated the risk of developing basal cell carcinoma (OR = 1.312) and melanoma (OR = 1.311). Sensitivity analyses did not alter the primary results. ConclusionTherefore, this study aimed to evaluate the potential and efficacy of SNP-based IL-6R blockade in treating cancer.

U2AF1 pathogenic variants in myeloid neoplasms and precursor states: distribution of co-mutations and prognostic heterogeneity

We have previously recognized the genotypic and prognostic heterogeneity of U2AF1 mutations (MT) in myelofibrosis (MF) and myelodysplastic syndromes (MDS). In the current study, we considered 179 U2AF1-mutated patients with clonal cytopenia of undetermined significance (CCUS; n = 22), MDS (n = 108), MDS/acute myeloid leukemia (AML; n = 18) and AML (n = 31). U2AF1 variants included S34 (60%), Q157 (35%), and others (5%): corresponding mutational frequencies were 45%, 55%, and 0% in CCUS; 57%, 39%, and 4% in MDS; 61%, 33%, and 6% in MDS/AML; and 55%, 35% and 10% in AML (P = 0.17, 0.36 and 0.09), respectively. Concurrent mutations included ASXL1 (37%), BCOR (19%), RUNX1 (14%), TET2 (15%), DNMT3A (10%), NRAS/KRAS (8%), TP53 (8%), JAK2 (5.5%) and SETBP1 (5%). The two most frequent U2AF1 MT were S34F (n = 97) and Q157P (n = 46); concurrent MT were more likely to be seen with the latter (91% vs 74%; P = 0.01) and abnormal karyotype with the former (70% vs 62%; P = 0.05). U2AF1 S34F MT clustered with BCOR (P = 0.04) and Q157P MT with ASXL1 (P = 0.01) and TP53 (P = 0.03). The median overall survival (OS) in months was significantly worse in AML (14.2) vs MDS/AML (27.3) vs MDS (33.7; P = 0.001); the latter had similar OS with CCUS (30.0). In morphologically high-risk disease (n = 49), defined by ≥10% blood or bone marrow blasts (i.e., AML or MDS/AML), median OS was 14.2 with Q157P vs 37.1 months in the presence of S34F (P = 0.008); transplant-adjusted multivariable analysis confirmed the detrimental impact of Q157P (P = 0.01) on survival and also identified JAK2 MT as an additional risk factor (P = 0.02). OS was favorably affected by allogeneic hematopoietic stem cell transplantation (HR: 0.16, 95% CI; 0.04-0.61, P = 0.007). The current study defines the prevalence and co-mutational profiles of U2AF1 pathogenic variants in AML, MDS/AML, MDS, and CCUS, and suggests prognostic heterogeneity in patients with ≥10% blasts.

O-119 - Cutaneous manifestation of mature plasmacytoid dendritic cell proliferation in patients with myeloid leukemia

O-119 - Cutaneous manifestation of mature plasmacytoid dendritic cell proliferation in patients with myeloid leukemia

Myeloablative fractionated busulfan for allogeneic stem cell transplant in older patients or patients with comorbidities

AbstractTraditional conditioning regimens for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) provide suboptimal outcomes, especially for older patients and those with comorbidities. We hypothesized that a fractionated myeloablative busulfan dose delivered over an extended period would reduce nonrelapse mortality (NRM) while retaining antileukemic effects. Here, we performed a phase 2 trial for adults with hematological malignancies receiving matched related or unrelated allo-HCT. Participants received busulfan 80 mg/m2 as outpatients on days −20 and −13 before transplant. Fludarabine 40 mg/m2 was administered on days −6 to −3, followed by busulfan dosed to achieve a target area under the curve of 20 000 mol/min for the whole course. The primary end point was day-100 NRM. Seventy-eight patients were included, with a median age of 61 years (range, 39-70 years), who received transplantation for acute leukemia (24%), myelodysplastic syndrome (27%), or myeloproliferative disease/chronic myeloid leukemia (44%). HCT-specific comorbidity index (HCT-CI) was ≥3 in 34 (44%). With a median follow-up of 36.4 months (range, 2.9-51.5), the 100-day, 1-year, and 3-year NRM rates were 3.8%, 8%, and 9.3%, respectively, without a significant difference in age or HCT-CI score. The 1-year and 3-year relapse incidence was 10% and 18%, respectively. The 3-year overall survival was 80%, without a significant difference in age or HCT-CI score and was similar for patients aged >60 years and those aged <60 years as well as for those with HCT-CI ≥3 and HCT-CI <3. Overall, a myeloablative fractionated busulfan regimen has low NRM without an increase in relapse rate, resulting in promising survival, even in older patients or in patients with comorbidities. This trial was registered at www.clinicaltrials.gov as #NCT02861417.

Precision Deuteration in Search of Anticancer Agents: Approaches to Cancer Drug Discovery.

Cancer chemotherapy has been shifted from conventional cytotoxic drug therapy to selective and target-specific therapy after the findings about DNA changes and proteins that are responsible for cancer. A large number of newer drugs were discovered as targeted therapy for particular types of neoplastic disease. The initial discovery includes the development of the first in the category, imatinib, a Bcr-Abl tyrosine kinase inhibitor (TKI) for the treatment of chronic myelocytic leukemia in 2001. But the joy did not last for long as the drug developed a point mutation within the ABL1 kinase domain of BCR-ABL1, which subsequently led to the discovery of many other TKIs. Resistance was observed for newer TKIs a few years after their launching, but the use of TKIs in life-threatening cancer therapy is considered as far better compared with the risks of disease because of its target specificity and hence less toxicity. In search of a better anticancer agent, the physiochemical properties of the lead molecule have been modified for its efficacy toward disease and delay in the development of resistance. Deuteration in the drug molecule is one of such modifications that alter the pharmacokinetic properties, generally its metabolism, as compared with its pharmacodynamic effects. Precision deuteration in many anticancer drugs has been carried out to search for better drugs for cancer. In this review, the majority of anticancer drugs and molecules for which deuteration was applied to get better anticancer molecules were discussed. This review will provide a complete guide about the benefits of deuteration in cancer chemotherapy.

Register-based and genetic studies of Prader-Willi syndrome show a high frequency of gonadal tumors and a possible mechanism for tumorigenesis through imprinting relaxation.

Prader-Willi syndrome (PWS) is a rare disease caused by a lack of expression of inherited imprinted genes in the paternally derived Prader-Willi critical region on chromosome 15q11.2-q13. It is characterized by poor feeding and hypotonia in infancy, intellectual disability, behavioral abnormalities, dysmorphic features, short stature, obesity, and hypogonadism. PWS is not a known cancer predisposition syndrome, but previous investigations regarding the prevalence of cancer in these patients suggest an increased risk of developing specific cancer types such as myeloid leukemia and testicular cancer. We present the results from a Swedish national population-based cohort study of 360 individuals with PWS and 18,000 matched comparisons. The overall frequency of cancer was not increased in our PWS cohort, but we found a high frequency of pediatric cancers. We also performed whole-genome sequencing of blood- and tumor-derived DNAs from a unilateral dysgerminoma in a 13-year-old girl with PWS who also developed bilateral ovarian sex cord tumors with annular tubules. In germline analysis, there were no additional findings apart from the 15q11.2-q13 deletion of the paternal allele, while a pathogenic activating KIT mutation was identified in the tumor. Additionally, methylation-specific multiplex ligation-dependent probe amplification revealed reduced methylation at the PWS locus in the dysgerminoma but not in the blood. In conclusion, our register-based study suggests an increased risk of cancer at a young age, especially testicular and ovarian tumors. We found no evidence of a general increase in cancer risk in patients with PWS. However, given our limited observational time, further studies with longer follow-up times are needed to clarify the lifetime cancer risk in PWS. We have also described the second case of locus-specific loss-of-imprinting in a germ cell tumor in PWS, suggesting a possible mechanism of carcinogenesis.

Trends in risk for therapy-related myelodysplastic syndrome/acute myeloid leukemia after initial chemo/immunotherapy for common and rare lymphoid neoplasms, 2000-2018.

Historically, survivors of common lymphoid neoplasms (LNs) had increased risks for therapy-related myelodysplastic syndrome/acute myeloid leukemia (tMDS/AML). Despite major treatment advances in the treatment of LNs over the last two decades, a comprehensive evaluation of tMDS/AML trends following both common and rare LNs treated in this contemporary period is lacking. In US cancer registries during 2000-2018, we identified 1496 tMDS/AML cases among 186,503 adults who were treated with initial chemo/immunotherapy for first primary LN and survived ≥1 year. We quantified tMDS/AML standardized incidence ratios (SIRs), excess absolute risks (EARs, per 10,000 person-years), and cumulative incidence. The highest tMDS/AML risks occurred after precursor leukemia/lymphoma (SIR=39, EAR=30), Burkitt leukemia/lymphoma (SIR=20, EAR=24), peripheral T-cell lymphoma (SIR=12, EAR=23), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; SIR=9.0, EAR=27), and mantle cell lymphoma (SIR=8.5, EAR=25). Elevated risks (SIRs=4.2-6.9, EARs=4.9-15) also were observed after all other LN subtypes except hairy cell leukemia and mycosis fungoides/Sézary syndrome. Among patients treated more recently, tMDS/AML risks were significantly higher after CLL/SLL (SIR2000-2005=4.8, SIR2012-2017=10, Ptrend=0.0043), significantly lower after Hodgkin (SIR2000-2005=15, SIR2012-2017=6.3, Ptrend=0.024) and marginal zone (SIR2000-2005=7.5, SIR2012-2017=2.3, Ptrend=0.015) lymphomas, and non-significantly lower after mantle cell lymphoma (SIR2000-2005=10, SIR2012-2017=3.2, Ptrend=0.054), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (SIR2000-2005=6.9, SIR2012-2017=1.0, Ptrend=0.067), and plasma cell neoplasms (SIR2000-2005=5.4, SIR2012-2017=3.1, Ptrend=0.051). EAR and cumulative incidence trends generally were similar to SIR trends. Median survival after tMDS/AML was 8.0 months (interquartile range, 3.0-22.0). Although tMDS/AML risks are significantly elevated after initial chemo/immunotherapy for most LNs, patients treated more recently have lower tMDS/AML risks, except after CLL/SLL. Though rare, the poor prognosis following tMDS/AML emphasizes the importance of continued efforts to reduce treatment-associated toxicity. This research was supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. LMM, GMD, REC, and CBS verified the data, and all authors had access to the data and made the decision to submit for publication.

Biomolecular Condensates in Myeloid Leukemia: What Do They Tell Us?

Recent studies have suggested that several oncogenic and tumor-suppressive proteins carry out their functions in the context of specific membrane-less cellular compartments. As these compartments, generally referred to as onco-condensates, are specific to tumor cells and are tightly linked to disease development, the mechanisms of their formation and maintenance have been intensively studied. Here we review the proposed leukemogenic and tumor-suppressive activities of nuclear biomolecular condensates in acute myeloid leukemia (AML). We focus on condensates formed by oncogenic fusion proteins including nucleoporin 98 (NUP98), mixed-lineage leukemia 1 (MLL1, also known as KMT2A), mutated nucleophosmin (NPM1c) and others. We also discuss how altered condensate formation contributes to malignant transformation of hematopoietic cells, as described for promyelocytic leukemia protein (PML) in PML::RARA-driven acute promyelocytic leukemia (APL) and other myeloid malignancies. Finally, we discuss potential strategies for interfering with the molecular mechanisms related to AML-associated biomolecular condensates, as well as current limitations of the field.

Molecular docking analysis of MCL-1 inhibitors for breast cancer management.

Myeloid leukemia 1 (MCL-1), a BCL-2 protein family member, acts as an anti-apoptotic protein by interacting with pro-apoptotic BCL-2 proteins. Its overexpression is frequently observed in numerous cancer types including breast cancer, and is closely linked to the initiation and progression of tumors as well as poor prognosis and resistance to therapeutic interventions. Here, a database of 3402 chemicals with established therapeutic activity against various diseases was chosen and systematically screened against the MCL-1 protein. Visual inspection and binding energy analysis revealed that the compounds OSU-03012, Raltitrexed, Ostarine (MK-2866), Dovitinib (TKI-258), and Varespladib (LY315920) had strong binding affinity for the MCL-1 protein. Notably, their binding affinity was higher than that of the control compounds. These compounds exhibited strong interactions with critical amino acid residues of the MCL-1 protein. Furthermore, these compounds shared several common amino acid residue interactions with the control compounds. These findings suggest that these compounds may be useful as MCL-1 inhibitors in the treatment of breast cancer. However, additional experimental validation is required to confirm these findings.

The incidence of selected neoplastic diseases among children and adolescents in the Silesian Voivodeship

Introduction.The causes of malignant neoplasms occurring in both children and adolescents remain unknown, but epidemiological and genetic studies have partially elucidated the origin of these tumors. Brain tumors are most common in children under 5 years of age. Mostly adolescents aged 10-14 years develop lymphomas and bone tumors. Objective. The aim of the article is to discuss the incidence of selected neoplastic diseases in children and adolescents from the Silesian Voivodeship in 2010-2019. The article includes: lymphocytic leukemia (C 91), myeloid leukemia (C 92), cancer of the brain and central nervous system (D 43) and non-Hodgkin's lymphoma (C82-85). Materials and methdos.In March 2022, data on the incidence (absolute numbers) of selected neoplastic diseases among children and adolescents from 0 to 19 years of age (divided into age groups: under 1, 1 to 4, 5 to 14 and 15 to 19) life) from the Silesian Voivodeship.Then, appropriate tables illustrating the incidence of the diseases in question were drawn up. Results.In the age group between 5 and 14 years of age, the incidence of lymphocytic leukemia increased between 2010 and 2013 and amounted to 30 in 2010 and 39 in 2013, respectively. tumors of the brain and central nervous system in 2011, in the years 2012-2014 the incidence was 7 cases per year, and from 2015 to 2019 the nature of the incidence increased and amounted to 8 in 2015 and 19 in 2019, respectively. Conclusions.One of the reasons adversely affecting the diagnostic and therapeutic process is the rarity of these diseases in the pediatric population, which makes it difficult for GPs to acquire their own professional experience in a short time. The second diagnostic difficulty is the different histological structure of tumors in children and adolescents.