Trends in childhood leukemia incidence in urban countries and their relation to environmental factors, including space weather.

Leukemia is the most common cancer in children. Its incidence has been increasing worldwide since 1910th, suggesting the presence of common sources of the disease, most likely related to people's lifestyle and environment. Understanding the relationship between childhood leukemia and environmental conditions is critical to preventing the disease. This discussion article examines established potentially-carcinogenic environmental factors, such as vehicle emissions and fires, alongside space weather-related parameters like cosmic rays and the geomagnetic field. To discern the primary contributor, we analyze trends and annual variations in leukemia incidence among 0-14-year-olds in the United States, Canada, Australia, and Russia from 1990 to 2018. Comparisons are drawn with the number of vehicles (representing gasoline emissions) and fire-affected land areas (indicative of fire-related pollutants), with novel data for Russia introduced for the first time. While childhood leukemia incidence is rising in all countries under study, the rate of increase in Russia is twice that of other nations, possibly due to a delayed surge in the country's vehicle fleet compared to others. This trend in Russia may offer insights into past leukemia levels in the USA, Canada, and Australia. Our findings highlight vehicular emissions as the most substantial environmental hazard for children among the factors examined. We also advocate for the consideration of potential modulation of carcinogenic effects arising from variations in cosmic ray intensity, as well as the protective role of the geomagnetic field. To support the idea, we provide examples of potential space weather effects at both local and global scales. The additional analysis includes statistical data from 49 countries and underscores the significance of the magnetic field dip in the South Atlantic Anomaly in contributing to a peak in childhood leukemia incidence in Peru, Ecuador and Chile. We emphasize the importance of collectively assessing all potentially carcinogenic factors for the successful future predictions of childhood leukemia risk in each country.

Substrate Affinity Is Not Crucial for Therapeutic L-Asparaginases: Antileukemic Activity of Novel Bacterial Enzymes.

L-asparaginases are used in the treatment of acute lymphoblastic leukemia. The aim of this work was to compare the antiproliferative potential and proapoptotic properties of novel L-asparaginases from different structural classes, viz. EcAIII and KpAIII (class 2), as well as ReAIV and ReAV (class 3). The EcAII (class 1) enzyme served as a reference. The proapoptotic and antiproliferative effects were tested using four human leukemia cell models: MOLT-4, RAJI, THP-1, and HL-60. The antiproliferative assay with the MOLT-4 cell line indicated the inhibitory properties of all tested L-asparaginases. The results from the THP-1 cell models showed a similar antiproliferative effect in the presence of EcAII, EcAIII, and KpAIII. In the case of HL-60 cells, the inhibition of proliferation was observed in the presence of EcAII and KpAIII, whereas the proliferation of RAJI cells was inhibited only by EcAII. The results of the proapoptotic assays showed individual effects of the enzymes toward specific cell lines, suggesting a selective (time-dependent and dose-dependent) action of the tested L-asparaginases. We have, thus, demonstrated that novel L-asparaginases, with a lower substrate affinity than EcAII, also exhibit significant antileukemic properties in vitro, which makes them interesting new drug candidates for the treatment of hematological malignancies. For all enzymes, the kinetic parameters (Km and kcat) and thermal stability (Tm) were determined. Structural and catalytic properties of L-asparaginases from different classes are also summarized.

Leukemia Types and Subtypes Analysis: Epidemiological Age-Standardized Exploration in the Mexican Bajio Region.

Background and Objectives: Leukemia, characterized by abnormal leukocyte production, exhibits clonal origin from somatic mutations. Globally, it ranked 15th in cancer incidence in 2020, with higher prevalence in developing countries. In Mexico, it was the ninth most frequent cancer. Regional registries are vital for understanding its epidemiology. This study aims to analyze the prevalence and age-standardized incidence rates of leukemias in a tertiary care hospital in the Mexican Bajio region. Materials and Methods: Leukemia cases from 2008-2018 were analyzed, and 535 medical records were included in this study. The prevalence, distribution, and age-specific incidence rate of different types and subtypes of leukemia were determined according to sex and age groups. Results: Overall, 65.79% consisted of lymphocytic leukemia, 33.64% of myeloid leukemia, and 0.56% of monocytic leukemia. No significant sex-based differences were found, but age-specific patterns were observed. Leukemia distribution by age revealed significant associations. Lymphocytic leukemia dominated in the pediatric population, particularly acute lymphocytic leukemia, while myeloid leukemia shifted towards adulthood. Age-specific incidence patterns showed, first, that lymphocytic leukemia is the most common leukemia in pediatric ages, and second, there is a shift from acute lymphocytic leukemia dominance in pediatric ages to myeloid leukemia incidence in late adulthood, emphasizing nuanced epidemiological dynamics. Conclusions: Acute leukemia cases occurred with high prevalence in our study population, with a high incidence in pediatric and adulthood populations, especially for acute lymphocytic leukemia, showing a (<18 years) 153.8 age-standardized incidence rate in the pediatric group, while in the adult population, the age-standardized rate was 59.84. In the age-specific analysis, we found that the childhood group (5-9 years) were the most affected by acute lymphocytic leukemia in the pediatric population, while in the adult population, the early-adulthood group (15-29 years) were the most affected age group. In contrast, chronic myeloid leukemia affected both adults and the pediatric populations, while chronic lymphocytic leukemia and monocytic leukemia were exclusive to adults. The study underscores the need for tailored diagnostic, treatment, and preventive strategies based on age, contributing valuable insights into the leukemia epidemiology of the Bajio region.

CD44: a cancer stem cell marker and therapeutic target in leukemia treatment.

CD44 is a ubiquitous leukocyte adhesion molecule involved in cell-cell interaction, cell adhesion, migration, homing and differentiation. CD44 can mediate the interaction between leukemic stem cells and the surrounding extracellular matrix, thereby inducing a cascade of signaling pathways to regulate their various behaviors. In this review, we focus on the impact of CD44s/CD44v as biomarkers in leukemia development and discuss the current research and prospects for CD44-related interventions in clinical application.

(2,6-Dimethylphenyl)arsonic Acid Induces Apoptosis through the Mitochondrial Pathway, Downregulates XIAP, and Overcomes Multidrug Resistance to Cytostatic Drugs in Leukemia and Lymphoma Cells In Vitro.

Cancer treatment is greatly challenged by drug resistance, highlighting the need for novel drug discoveries. Here, we investigated novel organoarsenic compounds regarding their resistance-breaking and apoptosis-inducing properties in leukemia and lymphoma. Notably, the compound (2,6-dimethylphenyl)arsonic acid (As2) demonstrated significant inhibition of cell proliferation and induction of apoptosis in leukemia and lymphoma cells while sparing healthy leukocytes. As2 reached half of its maximum activity (AC50) against leukemia cells at around 6.3 µM. Further experiments showed that As2 overcomes multidrug resistance and sensitizes drug-resistant leukemia and lymphoma cell lines to treatments with the common cytostatic drugs vincristine, daunorubicin, and cytarabine at low micromolar concentrations. Mechanistic investigations of As2-mediated apoptosis involving FADD (FAS-associated death domain)-deficient or Smac (second mitochondria-derived activator of caspases)/DIABLO (direct IAP binding protein with low pI)-overexpressing cell lines, western blot analysis of caspase-9 cleavage, and measurements of mitochondrial membrane integrity identified the mitochondrial apoptosis pathway as the main mode of action. Downregulation of XIAP (x-linked inhibitor of apoptosis protein) and apoptosis induction independent of Bcl-2 (B-cell lymphoma 2) and caspase-3 expression levels suggest the activation of additional apoptosis-promoting mechanisms. Due to the selective apoptosis induction, the synergistic effects with common anti-cancer drugs, and the ability to overcome multidrug resistance in vitro, As2 represents a promising candidate for further preclinical investigations with respect to refractory malignancies.

Health locus of control and symptom distress: The mediating role of illness acceptance and symptom severity in acute leukemia patients.

OBJECTIVE: This study aims to explore the multiple mediating roles of illness acceptance and symptom severity between health locus of control and symptom distress in acute leukemia patients. METHODS: From June 2022 to March 2023, a convenience sampling method was used to recruit 208 acute leukemia patients in the inpatient center of a hospital in Hebei. The Chinese versions of Multidimensional Health Locus of Control Scale, Illness Acceptance Scale, and Anderson Symptom Assessment Scale was used in the cross-sectional study. RESULTS: All participants reported the presence of symptom distress. Symptom distress was significantly correlated with chance health locus of control, illness acceptance, and symptom severity (P＜0.05). Illness acceptance alone played a mediating role in the relationship between chance health locus of control and symptom distress in acute leukemia patients (ß=0.087, 95%CI 0.030-0.167). The indirect role of chance health locus of control on symptom distress through symptom severity alone was also statistically significant (ß=0.131, 95%CI 0.008-0.252). Furthermore, the multiple mediating role of chance health locus of control and symptom distress through illness acceptance and symptom severity combined was verified (ß=0.027, 95%CI 0.001-0.089). The alternative model is also valid, indicating bidirectional relationships between symptom severity, illness acceptance, and chance health locus of control, collectively influencing symptom distress. CONCLUSION: There is a positive relationship between chance health locus of control and symptom distress; additionally, increasing social psychological interventions for illness acceptance and strengthening the management of core symptoms will help alleviate the impact of health chance locus of control on symptom distress in acute leukemia patients. Longitudinal studies are needed to confirm the causal relationships among the variables explored within the model. IMPACT ON NURSING PRACTICE: It is recommended that healthcare professionals pay attention to the assessment of health locus of control in patients, identify patients with health chance locus of control in a timely manner, take measures to enhance their disease acceptance, and strengthen the management of core symptoms, thereby reducing their level of symptom distress.

Illness cognition and associated socio-demographic and clinical factors in parents of children with leukemia.

PURPOSE: Illness cognition is an important mediator between psychological and behavioral adjustment and the quality of life for patients and their caregivers. Evidence related to illness cognition among parents of children with leukemia is limited. The purpose of this study is to explore the illness cognition status and associated factors in parents of children with leukemia. METHODS: A cross-sectional survey was conducted with the parents of 335 children with leukemia from three general children's hospitals in China from January to December 2022. A parents' version of the illness cognition questionnaire was used to collect data. This included three subscales: helplessness, acceptance, and perceived benefits. RESULTS: The mean scores of helplessness, acceptance and perceived benefits of parents regarding their children's disease were 15.56 (4.60), 16.25 (4.41), and 19.96 (3.69) respectively. The multiple regression model indicated seven factors associated with the parents' illness cognition (adjusted R [2] ranged from 0.182 to 0.134): four socio-demographic factors (parent's age, role, education level, and family income) and three clinical factors (length of time spent each day caring for the child, the child's age at diagnosis, and the duration of the disease). CONCLUSION: This study reports on different levels of illness cognition and associated factors among parents of children with leukemia. The results may help pediatric oncology medical staff identify risk factors for poor psychological adjustment to children's diseases. Parents may benefit from psychological support aimed at improving positive illness cognition.

Cd(II)-based complex loaded with drug doxorubicin hydrogels against leukemia and reinforcement learning.

A new 3D metal-organic frameworks [Cd6(L)4(bipy)3(H2O)2·H2O] (1) was gained by employing Cd(II) and organic ligand [H3L = 4,4',4''-(benzene-1,3,5-triyltris(oxy))tribenzoic acid)benzene acid; bipy = 4,4'-bipyridine] in the solvothermal condition, which has been fully examined via single-X ray diffraction, FTIR and elemental analysis and so on. Using natural polysaccharides hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) as raw materials, we successfully prepared HA/CMCS hydrogels and observed their internal micromorphology by scanning electron microscopy. Using doxorubicin (Dox) as a drug model, we synthesized a novel metal gel particle loaded with doxorubicin, and their encapsulation and release effects were studied using fluorescence spectroscopy, followed by further investigation of their components through thermogravimetric analysis. Based on this, the therapeutic effect on leukemia was evaluated. Finally, an enhanced learning method for automatically designing new ligand structures from host ligands was proposed. Through generative modeling and molecular docking simulations, the biological behavior of the host and predicted cadmium complexes was extensively studied.

Clinical Characteristics and Diagnosis of Ph-Positive Mixed Phenotype Acute Leukemia.

BACKGROUND: The goal was to improve the clinical cognition of Ph-positive mixed phenotype acute leukemia and avoid misdiagnosis or delayed diagnosis. METHODS: The clinical manifestations and laboratory results (bone marrow cell morphology, multiparameter flow cytometry, and cytogenetics) of a case of Ph-positive mixed phenotype acute leukemia were analyzed, and related literature was reviewed. RESULTS: Blood routine: WBC 386.35 x 109/L, HGB 117.00 g/L, PLT 31 x 109/L; 80% of the original cells can be seen by artificial classification. Morphological examination of bone marrow cells showed that the proliferation of nucleated cells was obviously active, and the original cells accounted for 76%. The size of the original cells was somewhat uniform, most of the cells had less mass, were stained light grayish blue, the cytoplasm particles were not obvious, the nuclei were mostly round or quasi-round, some of them showed distortion and nuclear notch, and the chromatin was coarse. Some of the cells were rich in mass, small azurin granules were seen, the nuclei were regular, most of them were round, the chromatin was fine, the myeloperoxidase and esterase staining were negative, the eosinophils accounted for 2.5%, and the basophils accounted for 0.5%. Flow cytometry immunotyping: Two groups of abnormal cells were seen in the bone marrow. 1. A group included 12.32% of nuclear cells and showed abnormal myeloid primitive cell phenotype. Main expression: CD117, CD34, CD38, HLA-DR, CD33, CD64, CD123, weak expression: CD13, CD19. 2. The other group included 45.61% of the nuclear cells and had a B-lymphoblastic phenotype. Main expression: CD34, CD38, HLA-DR, CD123, CD19, CD10, CD9, cCD79a, TDT, weak expression of CD13, CD22. Mixed phenotype acute leukemia (M/B) immunophenotype was considered. Chromosome: 46,XY,t(9; 22)(q34;q11.2) [20]. BCR-ABL (P210) fusion gene was positive. CONCLUSIONS: Mixed phenotype acute leukemia (MPAL) is a rare type of malignant hematologic disease. Its diagnosis is based on the comprehensive evaluation of bone marrow cell morphology, immunophenotype, molecular and cytogenetic features.

Drug Analysis of Voriconazole Combined with Granulocyte Colony Stimulating Factor.

BACKGROUND: The aim of the study was to improve the clinical cognition of leukemia-like reaction caused by voriconazole and granulocyte colony-stimulating factor and to avoid misdiagnosis or delayed diagnosis. METHODS: A case of drug analysis of Voriconazole combined with granulocyte colony stimulating factor was retrospectively analyzed and related literature was reviewed. RESULTS: Blood routine of the patient on July 29: WBC 13.48 x 109/L, neutrophil 85.3%, lymphocyte 13.4%, hemoglobin 111 g/L, platelet 285 x 109/L. Vancomycin was given to prevent intracranial infection. Lumbar puncture was performed on July 30, cerebrospinal fluid was sent for routine and biochemical examination, leukocytes were 0.15 x 109/L, monocytes 45%, polynuclear cells 55%, protein 1.172 g/L, Acinetobacter baumannii and Candida clorbicus were detected in sputum culture, vancomycin and meropenem static sites were given to prevent intracranial secondary infection. Fungi were detected in urine culture, and voriconazole was given to prevent fungal infection. Blood routine: White blood cell 0.61 x 109/L, neutrophil 23%, lymphocyte 73.8%, red blood cell 2.65 x 1012/L, hemoglobin 77 g/L, platelet 17 x 109/L, bone marrow was extracted after medication. Bone marrow images show poor myelodysplasia, with granulocytes dominated by protoearly cells. Subsequent flow cytometry, chromosomal karyotype, and fusion gene analysis were performed to exclude the possibility of leukemia. Flow cytometry showed that the proportion of myeloid primordial cells was not high, the granulocytes were mainly at the early and young stage, no abnormal phenotype was observed in erythrocytes, monocytes and NK cells, no obvious mature B lymphocytes were observed, and the ratio of CD4+/CD8+ was decreased. Karyotype results showed that there was no mitotic phase. The results of fusion gene analysis showed that the fusion gene was negative or lower than the detection sensitivity. Voliconazole was stopped first, and granulocyte colony stimulating factor was stopped 3 days later. Two weeks later, blood and bone marrow images basically recovered, white blood cell 7.88 x 109/L, neutrophil 46.3%, lymphocyte 48.2%, hemoglobin 126 g/L, platelet 142 x 109/L, bone marrow hyperplasia active. The proportion of three series is roughly normal. CONCLUSIONS: The reason for the occurrence of leukemia-like reaction in this patient was considered to be related to voriconazole and granulocyte colony stimulating factor, cessation of voriconazole and granulocyte colony stimulating factor, and recovery of blood and bone marrow images. In the clinical use of voriconazole and granulocyte colony stimulating factor, close attention should be paid to the drug interaction and individualized medication should be carried out to ensure the safety of medication.

Phytochemical study of Magonia pubescens A. St.-Hil. and cytotoxicity of branches aqueous extract on breast cancer and leukemia cells.

Magonia pubescens is a natural species from the Brazilian cerrado biome. Its fruits and seeds are used in the treatment of seborrheic dermatitis, a common inflammatory skin disease. In this work, the known compounds lapachol, stigmasterol, maniladiol and scopoletin were isolated from hexane and dichloromethane extracts of M. pubescens branches. The aqueous extract of this material was fractioned through a liquid-liquid partition and the obtained fractions were analyzed by UHPLC-MS/MS. The results obtained were compared with data from three databases, leading to the putative identification of 51 compounds from different classes, including flavonoids, saponins and triterpenes. The cytotoxicity of aqueous fractions was assayed against breast cancer (MDA-MB-231) and leukemia (THP-1 and K562) cells. The best activity was observed for fraction AE3 against MDA-MB-231 cells (IC50 30.72 µg.mL-1).

Frequency and Aberrant CD Marker Profile of Acute Leukaemias.

OBJECTIVE: To determine the frequency of different types of acute leukaemia and their subtypes along with associated aberrant CD markers. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Immunology Armed Forces Institute of Pathology, National University of Medical Sciences, Rawalpindi, Pakistan, from November 2021 to October 2023. METHODOLOGY: All samples received for flow cytometric immunophenotyping with suspicion of acute leukaemia were included in the study. Cells were stained with fluorochrome labelled monoclonal antibodies against lineage-specific cluster of differentiation (CD) markers through a lyse-wash procedure. Acquisition and analysis were done using multi-parameter BD FACS Canto II Flow cytometer and BD FACS Diva software, respectively. Data were entered and analysed using SPSS v 23.0. RESULTS: Over a period of 2 years, a total of 1,115 suspected patients were tested for acute leukaemia. Among them, 728 (65.3%) were males and 387 (34.7%) were females, with mean age 28 ± 21 years, ranging from 1 week to 87 years. Among a total of 875/1115 (78.5%) diagnosed cases of acute leukaemia, AML was the most common leukaemia present in 408/875 (46.6%) patients followed by B-ALL and T-ALL in 384/875 (43.8%) and 70/87 (8%) patients, respectively (p = 0.5712). Aberrant CD markers were detected in 109/875 (12.5%) leukaemias (p = 0.0628). The most common aberrant CD markers in B-ALL were CD13 and CD33 present in 30/384 (7.8%) cases separately. Among AML and T-ALL most common aberrant CD markers were CD7 and CD33 present in 25/408 (6.13%) and 7/70 (10%) cases, respectively. CONCLUSION: Special consideration should be given to the presence of aberrant CD markers when assigning lineages to acute leukaemias. They may be important diagnostic, prognostic, and management tools for institution of immunotherapy. KEY WORDS: Aberrant CD markers, Acute leukaemia, CD Markers, Flow cytometry, Immunophenotyping.

Impact of body mass index at diagnosis on outcomes of pediatric acute leukemia: A systematic review and meta-analysis.

BACKGROUND: The incidence of childhood malnutrition i.e., both obesity and undernutrition, is on a rise. While there is extensive evidence of the influence of body mass index (BMI) on the survival and other important outcomes of adult cancers, the impact of childhood BMI on one of the common pediatric cancers i.e., leukemia is not well studied. METHODS: Systematic search of PubMed, Scopus, and Google Scholar databases was done to identify studies that were conducted among pediatric patients with leukemia and had examined outcomes of interest based on BMI at the time of diagnosis. RESULTS: Effect sizes were reported as pooled hazards ratio (HR) along with 95% confidence intervals (CI). A total of 17 studies were included. Compared to pediatric leukemia patients with normal BMI, underweight (HR 1.07, 95% CI: 1.04, 1.11) and obese (HR 1.42, 95% CI: 1.18, 1.71) children with leukemia had higher risks of overall mortality. Underweight (HR 1.10, 95% CI: 1.02, 1.19) and obese (HR 1.34, 95% CI: 1.15, 1.55) pediatric leukemia patients had a tendency to lower event-free survival compared to children with normal BMI. The risk of relapse was not significant for underweight, overweight, and obese children. CONCLUSIONS: Both underweight and obese status at the time of diagnosis were associated with poor survival outcomes in pediatric patients with leukemia.

Sociodemographic factors and Child Opportunity Index disparities associated with missed care opportunities in pediatric patients with lymphoma and leukemia referred for FDG-PET/CT.

BACKGROUND: Little data exists on the association of missed care opportunities (MCOs) in children referred for nuclear medicine/nuclear oncology imaging examinations and socioeconomic disparities. OBJECTIVE: To determine the prevalence of MCOs in children with lymphoma/leukemia scheduled for fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and the impact of sociodemographic factors and Child Opportunity Index (COI). MATERIALS AND METHODS: Retrospective analysis of MCOs in children with lymphoma/leukemia scheduled for FDG-PET/CT (2012 to 2022) was performed. In univariate analysis, patient, neighborhood, and appointment data were assessed across MCOs and completed appointments. Logistic regression evaluated independent effects of patient-, neighborhood-, and appointment-level factors with MCOs. Two-sided P-value < .05 was considered statistically significant. RESULTS: In 643 FDG-PET/CT appointments (n = 293 patients; median age 15 years (IQR 11.0-17.0 years); 37.9% female), there were 20 MCOs (3.1%) involving 16 patients. Only 8.2% appointments involved Black/African American non-Hispanic/Latino patients, yet they made up a quarter of total MCOs. Patients living in neighborhoods with very low or low COI experienced significantly higher MCOs versus zip codes with very high COI (6.9% vs. 0.8%; P = 0.02). Logistic regression revealed significantly increased likelihood of MCOs for patients aged 18 to 21 [odds ratio (OR) 4.50; 95% CI 1.53-13.27; P = 0.007], Black/African American non-Hispanic/Latino (OR 3.20; 95% CI 1.08-9.49; P = 0.04), zip codes with very low or low COI (OR 9.60; 95% CI 1.24-74.30; P = 0.03), and unknown insurance status. CONCLUSION: Children with lymphoma/leukemia, living in zip codes with very low or low COI, and who identified as Black/African American non-Hispanic/Latino experienced more MCOs. Our study supports the need to address intersecting sociodemographic, neighborhood, and health system factors that will improve equitable access to necessary healthcare imaging for children.

Comparative analysis of the antimicrobial resistance and virulence traits in ESBL-producing-Klebsiella pneumoniae ST307 strains colonizing the gastrointestinal tract and causing a fatal bloodstream infection in a leukemia patient.

Klebsiella pneumoniae is an opportunistic pathogen that can colonize the gastrointestinal tract (GIT) of humans. The mechanisms underlying the successful translocation of this pathogen to cause extra-intestinal infections remain unknown, although virulence and antimicrobial resistance traits likely play significant roles in the establishment of infections. We investigated K. pneumoniae strains isolated from GIT colonization (strains Kp_FZcol-1, Kp_FZcol-2 and Kp_FZcro-1) and from a fatal bloodstream infection (strain Kp_HM-1) in a leukemia patient. All strains belonged to ST307, carried a transferable IncF plasmid containing the blaCTX-M-15 gene (pKPN3-307 TypeA-like plasmid) and showed a multidrug-resistance phenotype. Phylogenetic analysis demonstrated that Kp_HM-1 was more closely related to Kp_FZcro-1 than to the other colonizing strains. The Kp_FZcol-2 genome showed 81 % coverage with the Kp_HM-1 246,730 bp plasmid (pKp_HM-1), lacking most of its putative virulence genes. Searching public genomes with similar coverage, we observed the occurrence of this deletion in K. pneumoniae ST307 strains recovered from human colonization and infection in different countries. Our findings suggest that strains lacking the putative virulence genes found in the pKPN3-307 TypeA plasmid are still able to colonize and infect humans, highlighting the need to further investigate the role of these genes for the adaptation of K. pneumoniae ST307 in distinct human body sites.

Galectin-9, a pro-survival factor inducing immunosuppression, leukemic cell transformation and expansion.

Leukemia is a malignancy of the bone marrow and blood originating from self-renewing cancerous immature blast cells or transformed leukocytes. Despite improvements in treatments, leukemia remains still a serious disease with poor prognosis because of disease heterogeneity, drug resistance and relapse. There is emerging evidence that differentially expression of co-signaling molecules play a critical role in tumor immune evasion. Galectin-9 (Gal-9) is one of the key proteins that leukemic cells express, secrete, and use to proliferate, self-renew, and survive. It also suppresses host immune responses controlled by T and NK cells, enabling leukemic cells to evade immune surveillance. The present review provides the molecular mechanisms of Gal-9-induced immune evasion in leukemia. Understanding the complex immune evasion machinery driven by Gal-9 expressing leukemic cells will enable the identification of novel therapeutic strategies for efficient immunotherapy in leukemic patients. Combined treatment approaches targeting T-cell immunoglobulin and mucin domain-3 (Tim-3)/Gal-9 and other immune checkpoint pathways can be considered, which may enhance the efficacy of host effector cells to attack leukemic cells.

True Donor Cell Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: Diagnostic and Therapeutic Considerations-Brief Report.

Donor cell leukemia (DCL) is a rare complication after allogeneic hematopoietic stem cell transplantation (HSCT) accounting for 0.1% of relapses and presenting as secondary leukemia of donor origin. Distinct in phenotype and cytogenetics from the original leukemia, DCL's clinical challenge lies in its late onset. Its origin is affected by donor cell anomalies, transplant environment, and additional mutations. A 43-year-old woman, treated for early stage triple-negative breast cancer, developed mixed-phenotype acute leukemia (MPAL), 12 years later. Following induction chemotherapy, myeloablative conditioning, and allo-HSCT from her fully HLA-matched brother, she exhibited multiple cutaneous relapses of the original leukemia, subsequently evolving into DCL of the bone marrow. Cytogenetic analysis revealed a complex male karyotype in 20 out of 21 metaphases, however, still showing the MPAL phenotype. DCL diagnosis was confirmed by 90.5% XY in FISH analysis and the male karyotype. Declining further intensive chemotherapy including a second allo-HSCT, she was subsequently treated with repeated radiotherapy, palliative systemic therapies, and finally venetoclax and navitoclax but died seven months post-DCL diagnosis. This case underlines DCL's complexity, characterized by unique genetics, further complicating diagnosis. It highlights the need for advanced diagnostic techniques for DCL identification and underscores the urgency for early detection and better prevention and treatment strategies.