Hematopoietic Research Articles

EPO rs1617640 A>C is a Protective Factor for Chronic Obstructive Pulmonary Disease: A Case Control Study.

The occurrence and development of chronic obstructive pulmonary disease (COPD) are regulated by environmental and genetic factors. In hypoxia, Erythropoietin (EPO) satisfies the body's need for oxygen by promoting the production of red blood cells. Hypoxia was proven to be a common physiological condition in COPD progression and associated with many complications. Some studies have found that EPO is involved in the development of COPD. But the mechanism has not been fully proven. We conducted a case-control study enrolled 1095 COPD patients and 1144 healthy controls in Guangdong Province to evaluate the association between EPO polymorphisms (rs1617640 A>C, rs507392 A>G, rs564449 G>T) and COPD susceptibility. 872 participants from southern Gansu Province were recruited to verify the effect of EPO polymorphisms on lung function. EPO rs1617640 C allele reduced COPD susceptibility in southern Chinese significantly (AC vs. AA: adjusted Odds ratio (OR) = 0.805, 95% CI = 0.669-0.969; AC+CC vs. AA: adjusted OR = 0.822, 95% CI = 0.689-0.980). However, there was no association between rs507392 A>G and rs564449 G>T polymorphisms and COPD susceptibility (p > 0.05). We further observed that the rs1617640 C allele was associated with higher FEV1 and FVC in Guangdong and Gansu populations significantly (both p < 0.05). In brief, the level of FEV1 and FVC increased with the C allele number. We modeled the relative risk for men and women, in which the population-attributable risks chances were 0.449 (0.258-0.641) and 0.262 (0.128-0.396) respectively. In this model, smoking status, coal as fuels, education level, and rs1617640 A>C were finally retained for males, while smoking status, biomass as fuels, and1617640 A>C were retained for females. In the end, using the method developed by Gail and Bruzzi, we fitted a 10-year absolute risk model for southern Chinese with different individual relative risks, which was presented as a table. In conclusion, this study found that EPO rs1617640 A>C polymorphism is associated with COPD susceptibility in southern Chinese, and the C allele was associated with better lung function. In addition, it could also be considered a genetic marker associated with environmental factors to predict the absolute 10-year risk of COPD in southern Chinese.

Inflammation alters iron distribution in bone and spleen in mice.

Anemia of inflammation (or inflammation-associated anemia) decreases the quality of life in billions of patients suffering from various inflammatory diseases, such as infection, autoimmune diseases, and cancer, associated with a prolonged state of immune activation. While proper utilization of iron, a nutrient metal essential for erythropoiesis, is important for the prevention of anemia, the alteration of body iron homeostasis upon inflammation, which can contribute to the development of anemia, is not completely understood. Thus, we sought to examine temporal and spatial changes in the distribution of iron and iron-associated molecules during inflammation in mice. To induce inflammation, C57BL/6J mice were injected with turpentine oil weekly for 3 weeks, which resulted in anemia, decreased protein expression of ferroportin, a cellular iron exporter, in the spleen, duodenum, and liver, and increased iron stores in the duodenum and spleen. Tracer kinetic studies after oral administration of 59Fe revealed that more iron was found in the spleen and less in the femur bone in turpentine oil-injected mice compared to the saline-injected mice, indicating tissue-specific abnormalities in iron distribution during inflammation. However, there was no difference in the utilization of iron for red blood cell production after turpentine oil injection; instead, serum hemopexin level and lactate dehydrogenase activity were increased, suggesting increased red blood cell destruction upon inflammation. Our findings provide an improved understanding of temporal and spatial changes in the distribution and utilization of iron during inflammation.

Zinc and aging: a narrative review of the effects on hematopoiesis and its link with diseases.

There has been a global increase in the older population in recent decades and, as age advances, complex metabolic and epigenetic changes occur in the organism, and these may trigger some health complications commonly found among this population. Additionally, several changes occur in older people that can reduce the dietary intake or the process of nutrient absorption. In this way, tissues with high nutrient requirements are more affected. Hematopoiesis is the process of formation, development, and maturation of blood cells and is a process with a high turnover. This high demand makes the integrity of the hematopoietic process susceptible to various factors that impair physiological function, such as aging and micronutrient bioavailability. Among these micronutrients, Zinc is considered an important micronutrient, playing diverse roles across various tissues and cell types. Some of the alterations in hematopoiesis that appear as a consequence of aging and due to insufficient micronutrient intake are well described in the literature; however, not much is known about how zinc deficiency contributes towards the development of diseases seen in aging. Considering the importance of zinc to act on several biological processes, this narrative review discusses several studies related to the physiological requirements, deficiency, or excess of zinc, including studies in experimental models and humans, and aimed to shed light on the relationship between zinc and the regulation of hematopoietic tissue, exploring possible links between this mineral with common disorders that appear during aging.

Ppm1d truncating mutations promote the development of genotoxic stress-induced AML.

Hematopoietic stem cells (HSCs) ensure blood cell production during the life-time of an organism, and to do so they need to balance self-renewal, proliferation, differentiation, and migration in a steady state as well as in response to stress or injury. Importantly, aberrant proliferation of HSCs leads to hematological malignancies, and thus, tight regulation by various tumor suppressor pathways, including p53, is essential. Protein phosphatase magnesium-dependent 1 delta (PPM1D) is a negative regulator of p53 and promotes cell survival upon induction of genotoxic stress. Truncating mutations in the last exon of PPM1D lead to the production of a stable, enzymatically active protein and are commonly associated with clonal hematopoiesis. Using a transgenic mouse model, we demonstrate that truncated PPM1D reduces self-renewal of HSCs in basal conditions but promotes the development of aggressive AML after exposure to ionizing radiation. Inhibition of PPM1D suppressed the colony growth of leukemic stem and progenitor cells carrying the truncated PPM1D, and remarkably, it provided protection against irradiation-induced cell growth. Altogether, we demonstrate that truncated PPM1D affects HSC maintenance, disrupts normal hematopoiesis, and that its inhibition could be beneficial in the context of therapy-induced AML.

Developmental toxicity in early chicken embryos on exposure to an organophosphorus flame retardant, tris(2-chloroisopropyl) phosphate

Tris(2-chloroisopropyl) phosphate (TCIPP) is an organophosphate flame retardant detected in the environment and eggs, feathers, and livers. Early-developmental-stage avian embryos are vulnerable to the toxic effects of chemicals. However, studies on the specific effects of TCIPP on avian embryonic development are limited. We aimed to investigate the toxicity of TCIPP in early chicken embryos using a previously developed shell-less incubation system. Fertilized chicken (Gallus gallus domesticus) eggs (n = 220) were exposed to 50 or 500 nmol TCIPP/(g egg) or dimethyl sulfoxide (DMSO) as a vehicle control on Day 0 of incubation. Development of 198 embryos was monitored from Days 3–9 of incubation, and 22 embryos on Day 4 and 74 embryos on Day 9 were dissected. Messenger RNA expression levels for several genes were measured in embryos on Day 4. Both TCIPP-exposed groups showed a significant reduction in survival rate. Imaging analyses revealed significant decreases in body length, head and bill length, eye diameter, and forelimb and hindlimb length in both TCIPP-treated groups. TCIPP exposure significantly impaired the development of extraembryonic blood vessels and the production of red blood cells. A TCIPP-dose-dependent decreasing trend in heart rate was observed on Days 4–7. The somitic angle increased significantly on Days 4–6, and embryos with curved somites showed cleavage in the back and gaps between somites, resulting in asymmetrical somite formation. A significant correlation was found between the somitic angle and FGF8 expression levels, suggesting that TCIPP exposure affects somite formation through an altered FGF-signaling pathway. Embryos with somitic deformities in TCIPP-exposed groups had significantly reduced survival rates, indicating that abnormal segment formation directly increased mortality. Finally, eye weight and ocular luminosity values were significantly reduced, suggesting that TCIPP may also affect eye development. Overall, these findings highlight severe toxic effects of TCIPP on avian embryonic development, including in vascularization, cardiac function, and somite and ocular development.

Elevated CDKN1A (P21) mediates β-thalassemia erythroid apoptosis, but its loss does not improve β-thalassemic erythropoiesis

Abstractβ-thalassemias are common hemoglobinopathies due to mutations in the β-globin gene that lead to hemolytic anemias. Premature death of β-thalassemic erythroid precursors results in ineffective erythroid maturation, increased production of erythropoietin (EPO), expansion of erythroid progenitor compartment, extramedullary erythropoiesis, and splenomegaly. However, the molecular mechanism of erythroid apoptosis in β-thalassemia is not well understood. Using a mouse model of β-thalassemia (Hbbth3/+), we show that dysregulated expression of the FOXO3 transcription factor is implicated in β-thalassemia erythroid apoptosis. In Foxo3−/−/Hbbth3/+ mice, erythroid apoptosis is significantly reduced, whereas erythroid cell maturation, and red blood cell and hemoglobin production are substantially improved even with elevated reactive oxygen species in double-mutant erythroblasts. However, persistence of elevated reticulocytes and splenomegaly suggests that ineffective erythropoiesis is not resolved in Foxo3−/−/Hbbth3/+. We found the cell cycle inhibitor Cdkn1a (cyclin-dependent kinase inhibitor p21), a FOXO3 target gene, is markedly upregulated in both mouse and patient–derived β-thalassemic erythroid precursors. Double-mutant p21/Hbbth3/+ mice exhibited embryonic lethality with only a fraction of mice surviving to weaning. Notably, studies in adult mice displayed greatly reduced apoptosis and circulating Epo in erythroid compartments of surviving p21−/−/Hbbth3/+ mice relative to Hbbth3/+ mice, whereas ineffective erythroid cell maturation, extramedullary erythropoiesis, and splenomegaly were not modified. These combined results suggest that mechanisms that control β-thalassemic erythroid cell survival and differentiation are uncoupled from ineffective erythropoiesis and involve a molecular network including FOXO3 and P21. Overall, these studies provide a new framework for investigating ineffective erythropoiesis in β-thalassemia.

Hope on the Horizon: New and Future Therapies for Sickle Cell Disease.

This article provides an overview of conventional, new, and future treatment options for sickle cell disease (SCD), a genetic disorder affecting the production of hemoglobin. Current treatments include hydroxyurea, a conventional SCD treatment that increases the levels of fetal hemoglobin, and new treatments such as voxelotor, a recently approved SCD treatment that selectively binds hemoglobin, preventing formation of sickled red blood cells. In addition to discussing the mechanisms of action of current SCD treatments, potential side effects are also discussed, highlighting the need for new treatments that can address the limitations of current treatments and improve the quality of life for people with SCD. Future treatments, such as gene therapy, are also explored as promising treatment options for SCD patients.

The iron chaperone poly(rC)-binding protein 1 regulates iron efflux through intestinal ferroportin in mice

AbstractIron is an essential nutrient required by all cells but used primarily for red blood cell production. Because humans have no effective mechanism for ridding the body of excess iron, the absorption of dietary iron must be precisely regulated. The critical site of regulation is the transfer of iron from the absorptive enterocyte to the portal circulation via the sole iron efflux transporter, ferroportin. Here, we report that poly(rC)-binding protein 1 (PCBP1), the major cytosolic iron chaperone, is necessary for the regulation of iron flux through ferroportin in the intestine of mice. Mice lacking PCBP1 in the intestinal epithelium exhibit low levels of enterocyte iron, poor retention of dietary iron in enterocyte ferritin, and excess efflux of iron through ferroportin. Excess iron efflux occurred despite lower levels of ferroportin protein in enterocytes and upregulation of the iron regulatory hormone hepcidin. PCBP1 deletion and the resulting unregulated dietary iron absorption led to poor growth, severe anemia on a low-iron diet, and liver oxidative stress with iron loading on a high-iron diet. Ex vivo culture of PCBP1-depleted enteroids demonstrated no defects in hepcidin-mediated ferroportin turnover. However, measurement of kinetically labile iron pools in enteroids competent or blocked for iron efflux indicated that PCBP1 functioned to bind and retain cytosolic iron and limit its availability for ferroportin-mediated efflux. Thus, PCBP1 coordinates enterocyte iron and reduces the concentration of unchaperoned “free” iron to a low level that is necessary for hepcidin-mediated regulation of ferroportin activity.

Mutations in the bZip region of the CEBPA gene: A novel prognostic factor in patients with acute myeloid leukemia.

Hematopoiesis, the process of blood cell formation involves on a complex network of transcription factors. Among them, the CCAAT-enhancer-binding protein alpha (CEBPA) plays a crucial role in maintaining the balance between myeloid proliferation and differentiation. Imbalances in this network can lead to disrupted differentiation and contribute to the development of malignant diseases. Understanding of disease development and explore potential therapeutic strategies for hematological disorders associated CEPBA gen. The research involved a comprehensive analysis of CEBPA gene mutations in the context of acute myeloid leukemia (AML). This encompassed a thorough exploration of point mutations and double mutations in AML patients. In the context of acute myeloid leukemia (AML), mutations in the CEBPA gene, especially point mutations, are frequently observed. A significant number of AML patients present with double mutations in CEBPA, which have been linked to a more favorable prognosis in terms of overall survival and event-free survival. These patients also tend to exhibit enhanced responsiveness to treatment. Unraveling the intricate interplay of transcription factors, particularly CEBPA, holds significant implications for decoding the mechanisms governing hematopoiesis. This understanding offers a potential avenue for deciphering disease development and devising novel therapeutic strategies for hematological disorders. The findings underscore that CEBPA mutations correlate with enhanced overall survival and event-free survival, with relevance to those presenting within the bZip framework. This knowledge may contribute to advancing personalized treatments for hematological conditions.

Blood Parameter Profiles and Their Clinical Implications in Hypertensive Patients: A Retrospective Chart Review.

Introduction Hypertension (HTN) is a chronic condition that serves as a major risk factor for cardiovascular diseases, leading to increased mortality and morbidity. It is a frequent modifiable illness affecting global health, resulting in catastrophic fatalities and morbidity. Aim This study aims to investigate blood parameter profiles and their clinical implications in hypertensive patients at the Prince Faisal bin Khalid Cardiac Center in Abha, Saudi Arabia. Methods Utilizing retrospective data from 121 patients at the Prince Faisal bin Khalid Cardiac Center in Abha, Saudi Arabia. The hematological parameter examined were hemoglobin (HB), platelets, hematocrit (HCT), calcium, phosphorus, sodium, potassium, urea, creatinine, and uric acid. The SPSS version 28 software was used for data analysis. Results Significant correlations between various hematological parameters were found in the results, pointing to potential connections between kidney function, the production of blood cells, and electrolyte balance in hypertensive patients. The results align with earlier studies carried out in the area and offer insightful information for clinicians and researchers interested in managing HTN and its complications. Conclusion The study emphasized the significance of considering hypertensive patients' age, gender, and lifestyle when interpreting their blood parameter profiles. The findings imply that a thorough comprehension of these blood parameter values and their potential effects on HTN is necessary for effectively managing HTN in this population. This study on the blood parameter profiles in hypertensive patients in Saudi Arabia provides the relationships between various hematological parameter and their clinical implications. These findings should be considered when creating targeted interventions and strategies to address the specific requirements and difficulties of managing HTN and its associated complications in this population. More research is required to comprehend the underlying reasons for the observed variations in hematological parameter profiles and their effects on the management of HTN.

Oxidative Stress in Healthy and Pathological Red Blood Cells.

Red cell diseases encompass a group of inherited or acquired erythrocyte disorders that affect the structure, function, or production of red blood cells (RBCs). These disorders can lead to various clinical manifestations, including anemia, hemolysis, inflammation, and impaired oxygen-carrying capacity. Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense mechanisms, plays a significant role in the pathophysiology of red cell diseases. In this review, we discuss the most relevant oxidant species involved in RBC damage, the enzymatic and low molecular weight antioxidant systems that protect RBCs against oxidative injury, and finally, the role of oxidative stress in different red cell diseases, including sickle cell disease, glucose 6-phosphate dehydrogenase deficiency, and pyruvate kinase deficiency, highlighting the underlying mechanisms leading to pathological RBC phenotypes.

Context-dependent TGFβ family signalling in cell fate regulation.

The transforming growth factor-β (TGFβ) family are a large group of evolutionarily conserved cytokines whose signalling modulates cell fate decision-making across varying cellular contexts at different stages of life. Here we discuss new findings in early embryos that reveal how, in contrast to our original understanding of morphogen interpretation, robust cell fate specification can originate from a noisy combination of signalling inputs and a broad range of signalling levels. We compare this evidence with novel findings on the roles of TGFβ family signalling in tissue maintenance and homeostasis during juvenile and adult life, spanning the skeletal, haemopoietic and immune systems. From these comparisons, it emerges that in contrast to robust developing systems, relatively small perturbations in TGFβ family signalling have detrimental effects at later stages in life, leading to aberrant cell fate specification and disease, for example in cancer or congenital disorders. Finally, we highlight novel strategies to target and amend dysfunction in signalling and discuss how gleaning knowledge from different fields of biology can help in the development of therapeutics for aberrant TGFβ family signalling in disease.

Linking cell cycle to hematopoietic stem cell fate decisions.

Hematopoietic stem cells (HSCs) have the properties to self-renew and/or differentiate into any blood cell lineages. In order to balance the maintenance of the stem cell pool with supporting mature blood cell production, the fate decisions to self-renew or to commit to differentiation must be tightly controlled, as dysregulation of this process can lead to bone marrow failure or leukemogenesis. The contribution of the cell cycle to cell fate decisions has been well established in numerous types of stem cells, including pluripotent stem cells. Cell cycle length is an integral component of hematopoietic stem cell fate. Hematopoietic stem cells must remain quiescent to prevent premature replicative exhaustion. Yet, hematopoietic stem cells must be activated into cycle in order to produce daughter cells that will either retain stem cell properties or commit to differentiation. How the cell cycle contributes to hematopoietic stem cell fate decisions is emerging from recent studies. Hematopoietic stem cell functions can be stratified based on cell cycle kinetics and divisional history, suggesting a link between Hematopoietic stem cells activity and cell cycle length. Hematopoietic stem cell fate decisions are also regulated by asymmetric cell divisions and recent studies have implicated metabolic and organelle activity in regulating hematopoietic stem cell fate. In this review, we discuss the current understanding of the mechanisms underlying hematopoietic stem cell fate decisions and how they are linked to the cell cycle.

Molecular and clinical significance of FLT3, NPM1, DNMT3A and TP53 mutations in acute myeloid leukemia patients.

Acute myeloid leukemia (AML) is a type of blood cancer that affects the bone marrow and blood cells. AML is characterized by the rapid growth and accumulation of abnormal white blood cells, known as myeloblasts, which interfere with the production of normal blood cells. The main aim was to determine the relationship between these genetic alterations and the clinico-haematological parameters and prognostic factors with therapy for Iraqi patients with AML. We used Sanger Sequencing to detect the mutations in 76 AML patients. Clinical data of AML patients were retrospectively analysed to compare the prognosis of each gene mutation group. Somatic mutations were identified in 47.4% of the enrolled patients in a core set of pathogenic genes, including FLT3 (18 patients, 23.7%), DNMT3A (14, 18.4%), NPM1 (11, 14.5%) and TP53 (5, 6.8%). As multiple mutations frequently coexisted in the same patient, we classified patients into 10 further groups. Two novel mutations were detected in FLT3-ITD, with new accession numbers deposited into NCBI GenBank (OP807465 and OP807466). These two novel mutations were computationally analysed and predicted as disease-causing mutations. We found significant differences between patients with and without the detected mutations in disease progression after induction therapy (remission, failure and death; pv = < 0.001) and statistically significant differences were reported in total leukocyte count (pv = < 0.0001). These genes are among the most frequently mutated genes in AML patients. Understanding the molecular and clinical significance of these mutations is important for guiding treatment decisions and predicting patient outcomes.

Evaluation of splenic infarction ratio and platelet increase ratio after partial splenic artery embolization.

The spleen is part of the lymphatic system and is one of the least understood organs of the human body. It is involved in the production of blood cells and helps filter the blood, remove old blood cells, and fight infection. Partial splenic artery embolization (PSE) is widely used to treat pancytopenia and portal hypertension. The efficacy of PSE for improving thrombocytopenia has been well demonstrated. In this study, we evaluated the splenic infarction ratio and platelet increase ratio after PSE. Forty-five consecutive patients underwent PSE from January 2014 to August 2022. We retrospectively evaluated the splenic infarction volume and ratio after PSE and analyzed the relationship between the splenic infarction ratio and platelet increase ratio after PSE. The platelet increase ratio was correlated with the splenic infarction ratio after PSE. The cutoff value for the splenic infarction ratio with a two-fold platelet increase was 63.0%. We suggest performance of PSE in patients with a splenic infarction ratio of 63% to double the expected platelet count.

Transcription factor networks link B-lymphocyte development and malignant transformation in leukemia.

Rapid advances in genomics have opened unprecedented possibilities to explore the mutational landscapes in malignant diseases, such as B-cell acute lymphoblastic leukemia (B-ALL). This disease is manifested as a severe defect in the production of normal blood cells due to the uncontrolled expansion of transformed B-lymphocyte progenitors in the bone marrow. Even though classical genetics identified translocations of transcription factor-coding genes in B-ALL, the extent of the targeting of regulatory networks in malignant transformation was not evident until the emergence of large-scale genomic analyses. There is now evidence that many B-ALL cases present with mutations in genes that encode transcription factors with critical roles in normal B-lymphocyte development. These include PAX5, IKZF1, EBF1, and TCF3, all of which are targeted by translocations or, more commonly, partial inactivation in cases of B-ALL. Even though there is support for the notion that germline polymorphisms in the PAX5 and IKZF1 genes predispose for B-ALL, the majority of leukemias present with somatic mutations in transcription factor-encoding genes. These genetic aberrations are often found in combination with mutations in genes that encode components of the pre-B-cell receptor or the IL-7/TSLP signaling pathways, all of which are important for early B-cell development. This review provides an overview of our current understanding of the molecular interplay that occurs between transcription factors and signaling events during normal and malignant B-lymphocyte development.

Clinical Significance of Clonal Hematopoiesis

Clonal hematopoiesis (CH) is associated with somatic mutations of the hematopoietic stem cells responsible for red blood cell formation. The incidence of CH increases with age and negative environmental factors. It is particularly common in patients on chemotherapy, and is associated with a greater than 10-fold increased risk for hematological malignancy. It also increases the risk for cardiovascular disease. Despite recent advances in molecular and genetic research, the clinical and translational aspects of disease require more attention. However, as data accumulate, prevention of disease onset and progression will improve.

Review on Food Insecurity and its Relationship with Iron and Vitamin B12 Status Among Children

Iron and vitamin B12 are essential micronutrients needed for the growth and development of children. Iron is critical for erythropoiesis, notably in haemoglobin synthesis whereby haemoglobin transports oxygen to cells, which is essential for cellular metabolism and energy production. Meanwhile, vitamin B12 is required for deoxyribonucleic acid synthesis, intracellular metabolism, and blood cells formation and maturation. Lack of these essential micronutrients can lead to nutritional deficiency and anaemia, especially among children. Food insecurity is a condition where there is a lack of or uncertain availability of acquiring acceptable food. Food insecurity is associated with lower nutrient intake and micronutrient deficiencies including iron and vitamin B12, which can subsequently lead to poor health outcomes. Various determinants are associated with iron and vitamin B12 deficiency, and food insecurity, such as socio-economic factors, environmental factors, and dietary intake. This review will explore the possible relationship between iron, vitamin B12, and anaemia with food insecurity among children.

Kajian agro sosiologi dan potensi metabolit sekunder bunga telang (Clitoria ternatea) sebagai peningkat imunitas tubuh

In the context of agro-sociology, butterfly pea (Clitoria ternatea) is studied as one of the plants with high economic, health, and environmental value. Flower can be used as a raw material of herbal medicines that can improve human health, primarily in terms of immunity. The processing of secondary metabolites can help increase the added value of the pond farm itself. Some of the secondary metabolite compounds in strawberries that potentially boost the immune system among others are flavonoids, alkaloids and polyphenols. Flavonoid compounds including anthocyanins can help protect body cells from free radical damage and increase the production of white blood cells. Gulf flowers also contain alkaloids such as clitorine and cyanidine that have antimicrobial and antioxidant properties, thus helping inhibit the growth of bacteria and viruses that cause infections and diseases. Gulf flowers also contain polyphenols such as caffeic acid and chlorogenic acid that have anti-inflammatory and anti-cancer properties. With the potential of this secondary metabolite, the sustainable farming of strawflower continues to float in Indonesia, along with the awareness of a healthy lifestyle and back to nature of society.

Bone Marrow Changes in Septic Shock: A Comprehensive Review.

Septic shock is a life-threatening condition characterized by systemic inflammation resulting from a severe infection. Although the primary focus of sepsis research has traditionally been on the dysfunctional immune response, recent studies have highlighted the important role of bone marrow in the pathophysiology of septic shock. The bone marrow, traditionally regarded as the hematopoietic organ responsible for blood cell production, undergoes significant changes during sepsis, contributing to the overall immune dysregulation observed in this condition. This comprehensive review aims to provide a detailed overview of the bone marrow changes associated with septic shock. It explores the alterations in the bone marrow microenvironment, hematopoietic progenitor cells, and the subsequent effects on leukocyte production and function. Key cellular and molecular mechanisms involved in bone marrow dysfunction during septic shock are discussed, including the dysregulation of cytokines, chemokines, growth factors, and signaling pathways. Furthermore, this review highlights the clinical implications of bone marrow changes in septic shock. It emphasizes the impact of altered hematopoiesis on immune cell populations, such as neutrophils, monocytes, and lymphocytes, and their role in the progression and outcome of sepsis. The potential prognostic value of bone marrow parameters and the therapeutic implications of targeting bone marrow dysfunction are also addressed. The review summarizes relevant preclinical and clinical studies to comprehensively understand the current knowledge of bone marrow changes in septic shock. The limitations and challenges of studying bone marrow in the context of sepsis are acknowledged, and future directions for research are proposed.