Proliferation Of Lymphoid Cells Research Articles

A Case of Abdominal Discomfort for Long Duration

In our regular medical practice, we encounter a lot of patients with abdominal discomfort. Commonly every physician suspects this kind of symptoms as gaseous distension of gastro-intestinal tract or acidity. The most valuable thing is the proper physical examination to rule out any underlying pathology. Most common causes of epigastric pain are associated with gastritis, or hepatobiliary system and pancreas related disorders. Here we will describe a 47-year-old male patient who presented with abdominal discomfort for last 6 months. For last 2 months he developed an epigastric lump which was increasing in size and was associated with weight loss. After proper clinical evaluation and necessary relevant investigations, he was diagnosed having Non-Hodgkin’s Lymphoma (NHL). Non-Hodgkins Lymphoma represents monoclonal proliferation of lymphoid cells. The incidence of these tumors increases with age. Clinically the proliferation rate indicates whether it is a high- or low-grade tumor. The patient underwent some investigations like CT guided FNAC from the enlarged abdominal lymph node which confirmed high grade Non-Hodgkins Lymphoma and started with chemotherapy and responded well. As abdominal discomfort is one of the common complaints, we face during our regular medical practice so routine physical examination including abdominal examination is very crucial and informative for clinical diagnosis and Lymphoma is an important differential diagnosis in case of any abdominal lump. Bangladesh Crit Care J September 2024; 12 (2): 175-178

Composite Lymphoma Comprising of BCL2 Rearrangement Negative, CD23 Positive Follicle Center Cell Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Case Report

Abstract Introduction/Objective BCL2 rearrangement negative, CD23-positive follicle center cell lymphoma (BCL2 neg CD23 pos FCL) is a rare, recently described provisional entity in International Consensus Classification (2022). It has a predominantly diffuse growth pattern and often involves inguinal region. The molecular profile includes a high frequency of STAT6 and CREBBP co-mutation as well as 1q gain and a recurrent 1p36 loss/TNFRS14 abnormalities. We describe a composite tumor comprising of a rare entity BCL2 neg CD23 pos FCL and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL). To the best of our knowledge this is the first reported case description of this co-occurrence. Methods/Case Report A 59 y/o woman presented with right cervical and axillary lymphadenopathy (upto 1.6 cm). Sections showed partial effacement of nodal architecture by interfollicular and diffuse proliferation of atypical lymphoid cells. The interfollicular areas were comprised of a monotonous population of small lymphocytes. Immunohistochemical stains performed showed that the interfollicular CD20+ PAX5+ atypical lymphoid cells coexpressed CD5, CD23, BCL2 and LEF1 and were negative for CD10, BCL6, CD3, and SOX11, with MIB1 of 5-10%. Based on these, a diagnosis of CLL/SLL was made. Admixed with the CLL/SLL, a second neoplastic B-cell component that distorted nodal architecture was also identified. It composed of a diffuse proliferation of intermediate sized lymphoid cells with a centrocytic/centroblastic morphology. This smaller population of small to intermediate sized B cells expressed CD10, BCL6, and CD23 with a MIB1 proliferation index of ~30%. This population was CD5 and BCL2 negative. CD21 showed residual follicular dendritic cell meshworks. SOX11 and BCL1 were negative. Therefore, a diagnosis of BCL2 neg CD23 pos FCL was made. Flow cytometry showed two distinct populations of monotypic B-cells, one CD5-positive and the other CD10-positive. FISH studies were negative for BCL2 and BCL6 rearrangements as well as del1p36. Cytogenetics was positive for trisomy 12, supporting CLL/SLL. Next Generation Sequencing showed Tier 1 / 2 mutations in STAT6, TNFRSF14, CREBBP, and FOXO1, supporting BCL2 neg CD23 pos FCL. Hence, this represents a unique case of composite CLL/SLL and BCL2 neg CD23 pos FCL. B cell gene rearrangement showed 2 distinct clones confirming 2 separate B cell lymphomas. Results (if a Case Study enter NA) NA Conclusion Here, we describe a composite CLL/SLL and BCL2 rearrangement negative, CD23 positive, FCL never previously described in literature.

Structural and functional alterations in hematological parameters among individuals at clinically high risk for acute lymphocytic leukemia

Abstract: Acute lymphocytic leukemia (ALL) is a diverse category of hematological malignancies defined by the clonal proliferation of immature lymphoid cells. While advances in diagnostic procedures and treatment modalities have improved results for many patients, a group of them exhibit clinical characteristics that indicate a high risk of disease progression and unfavorable consequences. Understanding the underlying molecular processes and developing accurate prognostic indicators in this high-risk group is critical for personalized treatment approaches and better patient outcomes. Hematological markers, immunophenotyping profiles, and chromosomal defects in people who were clinically high risk (CHR) for ALL are discussed in this review. Alterations in hematological markers, such as elevated white blood cell counts, decreased hemoglobin levels, and thrombocytopenia, are indicative of the aggressive nature of high-risk ALL. Immunophenotyping investigations revealed abnormal expression patterns of lineage-specific markers, indicating clonal proliferation and differentiation arrest. Furthermore, cytogenetic examination revealed frequent chromosomal defects, such as the Philadelphia chromosome and hyperdiploidy, which have been linked to a poor prognosis in ALL patients. The combination of hematological, immunophenotypic, and cytogenetic data gives a thorough knowledge of disease biology and assists in risk assessment for patients with CHR for ALL. The present review elucidates the intricate interaction of hematological, immunophenotypic, and cytogenetic abnormalities in persons at clinically high risk for ALL, emphasizing the importance of integrated diagnostic techniques to enhance patient outcomes and optimize treatment strategies.

Епідеміологічні дані, етіологія, патогенез, фактори ризику, клінічні прояви, сучасні методи діагностики і лікування, прогнозування перебігу Неходжкінських лімфом (огляд літератури)

Non-Hodgkin lymphoma (NHL) is a group of malignant diseases characterized by clonal proliferation of lymphoid cells corresponding to different stages of differentiation of normal B- and T- lymphocytes or natural killer (NK) cells. NHL is histopathologically and clinically diverse and divided into two groups: B-cell lymphomas and T-cell lymphomas, and subtypes: indolent (slow) and aggressive, classic and extranodal. The etiology of NHL is environmental, infectious, immunological, iatrogenic and genetic factors. The pathogenesis of NHL consists in: 1) translocations of oncogenes; 2) cytogenetic aberrations and mutations of tumor suppressor genes. Clinical manifestations of NHL: 1) lymphadenopathy; 2) symptoms of the presence of an extranodal tumor (abdominal pain; jaundice; shortness of breath and/or pleural effusion; bleeding, symptoms of gastrointestinal obstruction; symptoms associated with infiltration by lymphoma cells of the skin, thyroid gland, salivary glands, etc.; neurological symptoms of central and/or peripheral origin); 3) symptoms of bone marrow infiltration; 4) general symptoms (fever, night sweats, weight loss, fatigue, loss of appetite). Diagnosis of NHL involves: 1) auxiliary research (histological, immunohistochemical, cytogenetic and molecular, use of more specific monoclonal antibodies, immunophenotypic diagnosis, gene sequencing); 2) diagnostic tactics (estimation of stage and determination of prognostic factors according to IPI); 3) differential diagnosis (covers other causes of symptoms). The choice of treatment program for NHL depends on the type of lymphoma and the patient's condition. The main methods of treatment: wait and watch; monotherapy with alkylating drugs; RT; combined РCT; combined РCT with the use of purine analogs; therapy with monoclonal antibodies; PCT+monoclonal antibodies; HDCT+THSC. Survival prognosis for NHL depends on the origin of the tumor and its stage.

B-cell lymphoma of the skin: clinical observation

Currently, there is an increase and an increase in the incidence of primary skin lymphomas worldwide. B-cell cutaneous lymphomas account for 25–30% of primary skin lymphomas. Among all skin lymphomas, primary cutaneous lymphoma from follicular center cells occurs in 10–11% of cases and is characterized by great diagnostic difficulties due to the great similarity of clinical manifestations with other dermatoses, such as benign lymphoplasia, Beck's sarcoidosis, Jessner–Kanof lymphocytic infiltration, skin metastases. This paper presents a clinical case of B-cell lymphoma in a 29-year-old woman with a lesion of the facial skin in the form of a node, initially incorrectly interpreted as benign lymphoplasia. For five years, the patient received therapy with topical glucocorticosteroids with no effect from. Subsequently, histological examination and immunohistochemistry were performed for the purpose of differential diagnosis of sarcoidosis with B-cell lymphoma. Histologically, there is nodular proliferation of atypical lymphoid cells in the dermis, most of which have cytological characteristics of a centrocyte with an admixture of a small number of central blasts. Nodular proliferates contain an admixture of compactly arranged small lymphocytes. There are no signs of epidermotropism. During immunohistochemical examination, cells forming nodular proliferates express CD20, bc16 with an index of proliferative activity for the expression of nuclear protein K167 ― 20–30%, a dissociated network of follicular dentritic cells expressing CD21 is determined at the base of nodular proliferates. They are not expressed by bc12, CD3, CD2, CD5 proliferate cells. CD117 is expressed by an admixture of discretely distributed mast cells. The morphological picture corresponds to primary cutaneous centrofollicular lymphoma. The node was excised. Radiation therapy was not prescribed due to the patient's pregnancy. This clinical observation highlights the importance of considering the diagnosis of lymphoma in the differential diagnosis of treatment-resistant dermatological diseases.

The Sentient Propagation-Reactive B Cell-Rich Lymphoid Proliferation

Reactive B cell-rich lymphoid proliferation is a heterogeneous group of non-neoplastic lymphoid cell proliferation recapitulating diverse B cell lymphomas. The lesion is commonly categorized as nodal and extra-nodal follicular proliferations, nodal and extra-nodal nodular proliferations or nodal and extra-nodal immunoblastic proliferations. Florid follicular hyperplasia is comprised of quantifiably enhanced, disseminated primary and secondary lymphoid follicles with irregular outlines. Hyperplastic Germinal Centres (GCs) are comprised of admixed centroblasts and centrocytes, reactive T cells, Follicular Dendritic Cells (FDCs) and tingible body macrophages. Lymph node architecture depicts lymphoid follicles comprised of cells expressing B cell antigens wherein primary follicles are pre-eminently constituted of small lymphocytes BCL2+, BCL6- and CD10- immune reactivity. Progressive Transformation of Germinal Centre (PTGC) is constituted of singular or few enlarged lymphoid follicles of 4x to 5x magnitude wherein mantle zone cells display extensive invagination into adjacent germinal centres. Hyaline Vascular Castleman’s Disease (HVCD) delineates innumerable lymphoid follicles confined to the lymph node cortex and medulla or diverse extramedullary sites.

Development of Epigenetic Modifiers with Therapeutic Potential in FMS-Related Tyrosine Kinase 3/Internal Tandem Duplication (FLT3/ITD) Acute Myeloid Leukemia and Other Blood Malignancies.

Blood cancers encompass a group of diseases affecting the blood, bone marrow, or lymphatic system, representing the fourth most commonly diagnosed cancer worldwide. Leukemias are characterized by the dysregulated proliferation of myeloid and lymphoid cells with different rates of progression (acute or chronic). Among the chronic forms, hairy cell leukemia (HCL) is a rare disease, and no drugs have been approved to date. However, acute myeloid leukemia (AML) is one of the most aggressive malignancies, with a low survival rate, especially in cases with FLT3-ITD mutations. Epigenetic modifications have emerged as promising strategies for the treatment of blood cancers. Epigenetic modulators, such as histone deacetylase (HDAC) inhibitors, are increasingly used for targeted cancer therapy. New hydroxamic acid derivatives, preferentially inhibiting HDAC6 (5a-q), were developed and their efficacy was investigated in different blood cancers, including multiple myeloma (MM), HCL, and AML, pointing out their pro-apoptotic effect as the mechanism of cell death. Among the inhibitors described, 5c, 5g, and 5h were able to rescue the hematopoietic phenotype in vivo using the FLT3-ITD zebrafish model of AML. 5c (leuxinostat) proved its efficacy in cells from FLT3-ITD AML patients, promoting marked acetylation of α-tubulin compared to histone H3, thereby confirming HDAC6 as a preferential target for this new class of hydroxamic acid derivatives at the tested doses.

Acute lymphoblastic leukaemia.

Acute lymphoblastic leukaemia (ALL) is a haematological malignancy characterized by the uncontrolled proliferation of immature lymphoid cells. Over past decades, significant progress has been made in understanding the biology of ALL, resulting in remarkable improvements in its diagnosis, treatment and monitoring. Since the advent of chemotherapy, ALL has been the platform to test for innovative approaches applicable to cancer in general. For example, the advent of omics medicine has led to a deeper understanding of the molecular and genetic features that underpin ALL. Innovations in genomic profiling techniques have identified specific genetic alterations and mutations that drive ALL, inspiring new therapies. Targeted agents, such as tyrosine kinase inhibitors and immunotherapies, have shown promising results in subgroups of patients while minimizing adverse effects. Furthermore, the development of chimeric antigen receptor T cell therapy represents a breakthrough in ALL treatment, resulting in remarkable responses and potential long-term remissions. Advances are not limited to treatment modalities alone. Measurable residual disease monitoring and ex vivo drug response profiling screening have provided earlier detection of disease relapse and identification of exceptional responders, enabling clinicians to adjust treatment strategies for individual patients. Decades of supportive and prophylactic care have improved the management of treatment-related complications, enhancing the quality of life for patients with ALL.

Integrated systems biology analysis of acute lymphoblastic leukemia: unveiling molecular signatures and drug repurposing opportunities.

Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by aberrant proliferation and accumulation of lymphoid precursor cells within the bone marrow. The tyrosine kinase inhibitor (TKI), imatinib mesylate, has played a significant role in the treatment of Philadelphia chromosome-positive ALL (Ph + ALL). However, the achievement of durable and sustained therapeutic success remains a challenge due to the development of TKI resistance during the clinical course.The primary objective of this investigation is to propose a novel and efficacious treatment approach through drug repositioning, targeting ALL and its Ph + subtype by identifying and addressing differentially expressed genes (DEGs). This study involves a comprehensive analysis of transcriptome datasets pertaining to ALL and Ph + ALL in order to identify DEGs associated with the progression of these diseases to identify possible repurposable drugs that target identified hub proteins.The outcomes of this research have unveiled 698 disease-related DEGs for ALL and 100 for Ph + ALL. Furthermore, a subset of drugs, specifically glipizide for Ph + ALL, and maytansine and isoprenaline for ALL, have been identified as potential candidates for therapeutic intervention. Subsequently, cytotoxicity assessments were performed to confirm the in vitro cytotoxic effects of these selected drugs on both ALL and Ph + ALL cell lines.In conclusion, this study offers a promising avenue for the management of ALL and Ph + ALL through drug repurposed drugs. Further investigations are necessary to elucidate the mechanisms underlying cell death, and clinical trials are recommended to validate the promising results obtained through drug repositioning strategies.

Characterisation of the tracheal transcriptional response of chickens to chronic infection with Mycoplasma synoviae

Mycoplasma synoviae causes infectious synovitis and respiratory tract infections in chickens and is responsible for significant economic losses in the poultry industry. Effective attachment and colonisation of the trachea is critical for the persistence of the organism and progression of the disease it causes. The respiratory tract infection is usually sub-clinical, but concurrent infection with infectious bronchitis virus (IBV) is known to enhance the pathogenicity of M. synoviae. This study aimed to explore differentially expressed genes in the tracheal mucosa, and their functional categories, during chronic infection with M. synoviae, using a M. synoviae-IBV infection model. The transcriptional profiles of the trachea were assessed 2 weeks after infection using RNA sequencing. In chickens infected with M. synoviae or IBV, only 1 or 8 genes were differentially expressed compared to uninfected chickens, respectively. In contrast, the M. synoviae-IBV infected chickens had 621 upregulated and 206 downregulated genes compared to uninfected chickens. Upregulated genes and their functional categories were suggestive of uncontrolled lymphoid cell proliferation and an ongoing pro-inflammatory response. Genes associated with anti-inflammatory effects, pathogen removal, apoptosis, regulation of the immune response, airway homoeostasis, cell adhesion and tissue regeneration were downregulated. Overall, transcriptional changes in the trachea, 2 weeks after infection with M. synoviae and IBV, indicate immune dysregulation, robust inflammation and a lack of cytotoxic damage during chronic infection. This model provides insights into the pathogenesis of chronic infection with M. synoviae.

Study of Patterns of Leukaemia in a Tertiary Care Hospital

Introduction: Leukaemia arises from abnormal proliferation of hematopoietic or lymphoid cells, categorized as acute or chronic and originating from lymphoid, myeloid, or mixed lineages. Clinical manifestations result from leukemic cell proliferation and tissue infiltration. Objectives: This study aimed to determine the frequency and clinicopathological profile of leukaemia cases. Material and Methods: A three-year cross-sectional observational study was carried out in the Department of Pathology, Indira Gandhi Medical College, Shimla. Diagnosis of Leukaemia was based on complete blood count, peripheral smear examination, bone marrow analysis and cytochemistry wherever required. Data comprising of patient details, clinical examination and haematological parameters were analysed. Results: A total of 163 leukaemia cases were identified, including 102 (63%) acute and 61(37%) cases of chronic leukaemia. Acute leukaemia consisted of 58 cases of Acute Myeloid Leukaemia (AML), 25 Acute Lymphoblastic Leukaemia (ALL), and 19 undifferentiated leukaemia (UL), while chronic cases comprised 47 Chronic Myeloid Leukaemia (CML) and 14 Chronic Lymphocytic Leukaemia (CLL). Most patients were in the age group of 31-60 years, with a male predominance (M:F 1.7:1). Conclusions: Early diagnosis and typing are vital for prompt leukaemia treatment. Despite advanced technologies, cytomorphological examination with cytochemistry remains crucial, especially in resource-limited settings like India. Keywords: Leukaemia, acute, chronic, cytomorphology, observational study

Telomerase Inhibition in the Treatment of Leukemia: A Comprehensive Review.

Leukemia, characterized by the uncontrolled proliferation and differentiation blockage of myeloid or lymphoid precursor cells, presents significant therapeutic challenges despite current treatment modalities like chemotherapy and stem cell transplantation. Pursuing novel therapeutic strategies that selectively target leukemic cells is critical for improving patient outcomes. Natural products offer a promising avenue for developing effective chemotherapy and preventive measures against leukemia, providing a rich source of biologically active compounds. Telomerase, a key enzyme involved in chromosome stabilization and mainly active in cancer cells, presents an attractive target for intervention. In this review article, we focus on the anti-leukemic potential of natural substances, emphasizing vitamins (such as A, D, and E) and polyphenols (including curcumin and indole-3-carbinol), which, in combination with telomerase inhibition, demonstrate reduced cytotoxicity compared to conventional chemotherapies. We discuss the role of human telomerase reverse transcriptase (hTERT), particularly its mRNA expression, as a potential therapeutic target, highlighting the promise of natural compounds in leukemia treatment and prevention.

Phosphatase, Mg2+/Mn2+ dependent 1B regulates the hematopoietic stem cells homeostasis via the Wnt/β-catenin signaling.

Hematopoietic stem cells (HSC) are primarily dormant in a cell-cycle quiescence state to preserve their self-renewal capacity and long-term maintenance. How HSC maintain the balance between activation and quiescence remains largely unknown. Herein, we found that phosphatase, Mg2+/Mn2+ dependent 1B (Ppm1b) is required for the expansion of phenotypic HSC in vitro. By using a conditional knockout mouse model in which Ppm1b was specifically depleted in hematopoietic cells, we demonstrated that loss of Ppm1b impaired the HSC homeostasis and hematopoietic reconstitution. Ppm1b deficiency mice also exhibited B-cell leukocytopenia, which is due to the compromised commitment and proliferation of B-biased lymphoid progenitor cells from common lymphoid progenitors. With the aid of a small molecular inhibitor, we confirmed the roles of Ppm1b in adult hematopoiesis that phenocopied the effects with loss of Ppm1b. Furthermore, transcriptome profiling of Ppm1b-deficient HSC revealed the disruptive quiescence of HSC. Mechanistically, Ppm1b interacted with β-catenin and mediated its dephosphorylation. Loss of Ppm1b led to the decrease in the active β-catenin (non-phosphorylated) that interrupted the Wnt/β-catenin signaling in HSC, which consequently suppressed HSC expansion. Together, our study identified an indispensable role for Ppm1b in regulating HSC homeostasis via the Wnt/β-catenin pathway.

Glycolysis Modulation by METTL7B Shapes Acute Lymphoblastic Leukemia Cell Proliferation and Chemotherapy Response.

Acute lymphoblastic leukemia (ALL) is a devastating hematological malignancy characterized by uncontrolled proliferation of immature lymphoid cells. While advances in treatment have improved patient outcomes, challenges remain in enhancing therapeutic efficacy and understanding underlying molecular mechanisms. Methyltransferase-like 7B (METTL7B), known for its methyltransferase activity, has been implicated in various solid tumors, yet its role in ALL remains unexplored. Here, we reveal that high METTL7B expression is correlated with poorer prognosis in ALL patients. Employing genetic manipulation strategies, we demonstrate that METTL7B depletion reduces ALL cell proliferation and enhances chemosensitivity. Mechanistically, we uncover METTL7B's involvement in modulating glycolysis, a crucial metabolic pathway supporting ALL cell growth. Furthermore, METTL7B's methyltransferase activity is identified as a determinant of its impact on glycolysis and proliferation. This study sheds light on METTL7B's multifaceted role in ALL, highlighting its potential as a therapeutic target and offering insights into the metabolic rewiring crucial for ALL progression.

Contribution of Computed Tomography in the Diagnosis of Multifocal Non-Hodgkin’s Lymphoma at the Mother-Child University Hospital the ‘’Luxembourg’’ About a Case

Lymphoma is a malignant proliferation of lymphoid tissue cells. We report a case of multi-focal lymphoma of lymph node, pharyngeal, cardiac and splenic sites. This was a 19-year-old patient received in February 2023, at the radiology and medical imaging department of the Mother and Child University Hospital Center ''Luxembourg'' as part of the CT exploration of a lateral mass. -left cervical. On admission, the clinical examination found a patient with an altered general condition, moderately colored conjunctiva, normal blood pressure and temperature. Examination of the lymph node areas revealed a left latero-cervical swelling, and fixed bilateral axillary swellings, of firm consistency and irregular contours. Palpation revealed hepatosplenomegaly. Cardiopulmonary auscultation was normal. A cervico-thoraco-abdominal CT scan revealed irregular thickening of the left lateral wall of the oropharynx, a hypodense tissue mass in the right cardiac chambers, heterogeneous splenomegaly, cervical, mediastinal, axillary and abdominal ADP. The histological examination carried out after lymph node biopsy revealed a histological appearance of small cell lymphoma. Conclusion: Lymphoma is a very common malignant tumor that can occur at any age. This tumor can affect all organs, however its cardiac location is rare. The positive diagnosis remains histological. Imaging plays an important role in the initial assessment, extension and surveillance.

Percutaneous Perirenal Mass Biopsy in a Sitting Position Revealed Extramedullary Relapse of Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is a blood malignancy characterized by a rapid proliferation of lymphoid progenitor cells. Extramedullary relapse (EMR) is the recurrence of leukemia that occurs outside the bone marrow. The central nervous system is the most prevalent site of EMR in ALL, whereas other organs, particularly the renal organs, are less commonly involved. A 49-year-old man diagnosed with Philadelphia chromosome-negative ALL (Ph-negative ALL) received a second umbilical cord blood transplant (uCBT) and was confirmed to be in his third hematological complete remission. However, the perirenal mass lesion emerged after two weeks, and was difficult to detect on echography in the prone position. We successfully performed a percutaneous biopsy of the mass in a sitting position and pathologically identified it as EMR. After the diagnosis, chemotherapy was restarted, and the patient was scheduled to receive a third uCBT. This is the first report of EMR in a perirenal lesion of ALL and shows that this novel biopsy can be performed as a renal biopsy, even in a sitting position. This case is the first to describe a biopsy technique in detail and demonstrates the value of collaboration between hematologists and nephrologists in diagnosing EMR of the kidneys.

Lateralized response of skull bone marrow via osteopontin signaling in mice after ischemia reperfusion

Skull bone marrow is thought to be an immune tissue closely associated with the central nervous system (CNS). Recent studies have focused on the role of skull bone marrow in central nervous system disorders. In this study, we performed single-cell RNA sequencing on ipsilateral and contralateral skull bone marrow cells after experimental stroke and then performed flow cytometry and analysis of cytokine expression. Skull marrow showed lateralization in response to stroke. Lateralization is demonstrated primarily by the proliferation and differentiation of myeloid and lymphoid lineage cells in the skull bone marrow adjacent to the ischemic region, with an increased proportion of neutrophils compared to monocytes. Analysis of chemokines in the skull revealed marked differences in chemotactic signals between the ipsilateral and contralateral skull, whereas sympathetic signals innervating the skull did not affect cranial bone marrow lateralization. Osteopontin (OPN) is involved in region-specific activation of the skull marrow that promotes inflammation in the meninges, and inhibition of OPN expression improves neurological function.Graphical

Phase Angle and Body Composition As a Prognostic Factor in Acute Lymphoblastic Leukemia

Acute lymphoblastic leukaemia (ALL) is a malignant proliferation of lymphoid cells blocked at an early stage of differentiation that can invade bone marrow, blood, and extramedullary sites. Age specific incidence is highest in children aged 1-4 years, then drops sharply through childhood (5-14 years), adolescence and young adulthood (AYA) (15-39 years), reaching the lowest point between 25 years and 45 years. Bioelectrical impedance analysis (BIA) is a method used to estimate body composition and cell membrane integrity. BIA is a useful tool as it is non-invasive, relatively inexpensive, can be performed on nearly any patient, does not expose the patient to ionizing radiation, is painless, and has both high intra and inter observer precision (coefficient of variation = 2.7%-4.0%). Phase angle (PhA) is obtained by BIA and is associated with cellular function. It is considered a reliable marker of malnutrition. PhA has been shown to predict survival in solid malignancies and hematopoietic stem cell transplant patients. To date, no studies have evaluated the usage of PhA in ALL patients. Therefore, this retrospective study sought to establish the prognostic significance of baseline PhA and lean mass index on OS and LFS in newly diagnosed ALL patients receiving intensive chemotherapy. Retrospective, cross-section, observational and descriptive study. The records of patients who received intensive chemotherapy from January 2019 to January 2023 were reviewed. Statistical analysis The qualitative variables were studied in frequencies and proportions, the quantitative variables were grouped into medians and ranges. OS and LFS were determined using Kaplan-Meier survival curves with log-Rank with a significant p <0.05 value. Statistical analysis was performed with SPSS version 25 and GraphPad Prism version 9.5.0. Results 85 patients were included, 56.7% (48) men and 43.5% (37) women. 79 patients with ALL-B and 6 patients ALL-T. The mean age was 25 years. 68 were AYA population and 17 not-AYA. The CR was 89%, ND MRD was 57%. The chemotherapy for AYA was CALGB 10403, and not AYA was Hyper-CVAD. Relapse was documented in 38%. The mean body mass index was 26.98±5.27 kg/m 2. The mean PhA was 4.547±0.9983°. The mean lean mass index was 17.8 (12.9-35.5) kg/m 2. The mean fat mass index was 9.195±4.425 kg/m 2. The mean OS was 86% at 1 year and OS at 3 years was 64.5%. The results that were statistically significant in LFS compared by Kaplan Meier curves were: male vs female p=0.0344, PhA >4, p=0.0235, lean mass index ≥16, p=0.0111. Conclusions In conclusion, our findings suggest that in newly diagnosed ALL patients undergoing intensive induction chemotherapy, PhA may provide important prognostic information for LFS and OS. PhA is an objective, repeatable, high-precision measure in ALL patients and, unlike other prognostic factors in this population, is potentially subject to intervention. Future studies of PhA in ALL patients should address the content validity of phase angle while further exploring the promising findings of the effect of strength training and nutritional supplementation on PhA and patient outcomes.

Causes of Acute Lymphoblastic Leukemia (All), Diagnosis and Treatment

Acute Lymphoblastic Leukemia (ALL) is a malignancy of the blood and bone marrow affecting both adults and children. Despite significant advancements in the treatment of ALL, its etiology remains multifactorial and complex. This scientific article aims to comprehensively explore the current understanding of the causes of ALL, integrating genetic, environmental, and other potential risk factors with the intent to enhance future research, exploring methods of diagnosis and treatment, and ultimately improve preventative measures and therapeutic strategies. Acute Lymphoblastic Leukemia (ALL) is characterized by the uncontrolled proliferation of immature lymphoid progenitor cells in the bone marrow. Although dramatic progress has been made in treating this disease, its etiology challenges scientists and clinicians alike. A better understanding of the underpinning causes of ALL is imperative to develop tailored interventions and preventive strategies. The etiology of Acute Lymphoblastic Leukemia remains a complex puzzle, tightly intertwined with a combination of genetic, environmental, and lifestyle factors. While significant progress has been made in identifying key genetic alterations and environmental exposures associated with ALL, further research is essential to understand the intricate interplay between genetic predispositions and environmental triggers. Improved understanding of the causes of ALL will aid in developing effective preventive strategies, targeted therapies, and personalized treatment approaches, ultimately reducing the burden of this devastating disease.

Significance of Th17 and Treg in Treatment Efficacy and Outcome in Pediatric Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia represents a malignant proliferation of lymphoid cells blocked at an early stage of cell differentiation. It is the most common cancer occurring in children. Despite favorable prognosis, the survival rate of patients with poor treatment response or relapse remains dismal. The interaction between leukemic cells and the tumor immune microenvironment is pivotal in mediating tumor progression. In this study we evaluated associations between Treg and Th17 lymphocytes and the clinical presentation of ALL pediatric patients to validate their value in monitoring treatment outcome. The peripheral blood and bone marrow aspirates from 35 pediatric patients with ALL and 48 healthy control subjects were selected for the experiment. We demonstrated the numbers of Th17 lymphocytes and Tregs were increased in the bone marrow of ALL patients at the moment of diagnosis compared to the healthy control group, with the latter significantly decreasing during the course of ALL treatment. Patients with lower Th17 were found to demonstrate higher risk of blasts prevalence in bone marrow at day 33. ALL patients with lower WBC demonstrated higher frequency of Tregs. In summary, we identified a significant role of Th17 and Treg lymphocytes in ALL of pediatric patients and their contribution to disease-related parameters.