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Scientific Reports May 2024Within the bloodstream, monocytes must traverse the microvasculature to prevent leukostasis, which is the entrapment of monocytes within the confines of the...
Within the bloodstream, monocytes must traverse the microvasculature to prevent leukostasis, which is the entrapment of monocytes within the confines of the microvasculature. Using the model cell line, THP-1, and VCAM-1 coated channels to simulate the microvasculature surface, we demonstrate that monocytes predominantly adopt an amoeboid phenotype, which is characterized by the formation of blebs. As opposed to cortical actin flow in leader blebs, cell movement is correlated with myosin contraction at the cell rear. It was previously documented that cofilin-1 promotes cortical actin turnover at leader bleb necks in melanoma cells. In monocytes, our data suggest that cofilin-1 promotes the local upregulation of myosin contractility through actin cytoskeleton remodeling. In support of this concept, cofilin-1 is found to localize to a single cell edge. Moreover, the widespread upregulation of myosin contractility was found to inhibit migration. Thus, monocytes within the microvasculature may avoid entrapment by adopting an amoeboid mode of migration.
Topics: Monocytes; Humans; Cofilin 1; Cell Movement; Actin Cytoskeleton; Myosins; Actins; Vascular Cell Adhesion Molecule-1; THP-1 Cells
PubMed: 38702365
DOI: 10.1038/s41598-024-60971-1 -
Cureus Mar 2024Leukostasis is a non-infectious complication of acute leukemia. Pathophysiologically, it is characterized by an accumulation of blasts in the pulmonary capillaries....
Leukostasis is a non-infectious complication of acute leukemia. Pathophysiologically, it is characterized by an accumulation of blasts in the pulmonary capillaries. Clinically, this syndrome of hyperleukocytosis or leucocytosis leads to pulmonary and/or neurological lesions. This is why it must be treated urgently to prevent it from progressing to acute respiratory distress. In 2020, the World Health Organization (WHO) declared a pandemic caused by a novel coronavirus called SARS-CoV-2, which may cause respiratory distress or other clinical, biological, and radiological signs that some may confuse with those of leukostasis. In this context, we present a compelling case study of a 64-year-old patient with no notable pathological antecedents and not vaccinated against COVID-19, who presented with acute respiratory distress. The purpose of our article is to succeed in differentiating between the two pneumopathies, thus making it possible to orient the doctor toward the right decision-making. As known, early recognition enables timely interventions, reducing disease progression and associated complications while also preventing unnecessary treatments, optimizing healthcare resources, and advancing medical knowledge for improved patient care in both acute leukemia and COVID-19 management.
PubMed: 38646395
DOI: 10.7759/cureus.56708 -
Cancers Dec 2023We aimed to identify subsets of patients who benefit from emergency LA and to establish a therapeutic algorithm for AML patients with hyperleukocytosis.
PURPOSE
We aimed to identify subsets of patients who benefit from emergency LA and to establish a therapeutic algorithm for AML patients with hyperleukocytosis.
METHODS
In this single-center retrospective cohort study, a total of 20 consecutive patients underwent LA because of their clinical symptoms. Overall survival (OS) analysis was conducted using the Kaplan-Meier plot method. Univariate and multivariate analyses (using multiple logistic regression) were performed. At the time of diagnosis, all patients received a standard diagnostic workup for AML including FLT3-ITD mutational analysis.
RESULTS
FLT3-ITD mut AML patients receiving LA had a median OS of 437 days (range 5-2379 days) with a corresponding 14-day survival of 92.3%, while FLT3 wt AML patients displayed a significantly lower median OS of only 5 days (range 1-203 days) with a corresponding 14-day survival of 14.3% ( = 0.0001).
CONCLUSIONS
Among patients with clinical symptoms of leukostasis, the subset of FLT3-ITD mut AML patients showed a better outcome with lower early mortality after emergency LA. Based on these observations, we established a therapeutic algorithm for AML patients with hyperleukocytosis.
PubMed: 38201486
DOI: 10.3390/cancers16010058 -
Cureus Dec 2023Acute myeloid leukemia (AML), the most common form of acute leukemia, is an aggressive lethal hematological malignancy that mainly occurs in older adults with a slightly...
Acute myeloid leukemia (AML), the most common form of acute leukemia, is an aggressive lethal hematological malignancy that mainly occurs in older adults with a slightly higher predominance in males. It is prompted by the clonal expansion of immature myeloid blasts in the bone marrow, peripheral blood, and/or extramedullary tissues. Leukostasis in AML is a critical medical condition mainly affecting the lungs and brain and arises when tissue perfusion is compromised due to the clustering of white blood cells (WBCs) within the microvasculature. Cardiac involvement in this condition is exceptionally uncommon. Here, we present a case of a 56-year-old man, recently diagnosed with acute myelogenous leukemia M4 and leukostasis, who developed acute anterior ST-elevation myocardial infarction six days after presentation and in whom emergent coronary angiography showed proximal left anterior descending (LAD) artery lesion with a large clot obstructing the flow and thrombolysis in myocardial infarction (TIMI) I flow, and urgent percutaneous coronary intervention (PCI) was done; thromboaspiration and drug-coated balloon angioplasty were performed with good angiographic results. Antiplatelet (aspirin and clopidogrel) and anticoagulation (enoxaparin) were started immediately before PCI. Emergent leukapheresis was initiated in addition to hydroxyurea with complete resolution of chest pain. Four days post PCI, the patient developed right-sided hemiparesis with an evident infarct on a CT scan of the brain, and he also developed acute limb ischemia involving the distal right foot. Five days post PCI, the patient had a sudden sustained ventricular tachycardia followed immediately by asystole, and cardio-pulmonary resuscitation was done for 25 minutes but with no response.
PubMed: 38077674
DOI: 10.7759/cureus.50230 -
Cells Nov 2023Optic neuritis, a characteristic feature of multiple sclerosis (MS), involves the inflammation of the optic nerve and the degeneration of retinal ganglion cells (RGCs)....
Optic neuritis, a characteristic feature of multiple sclerosis (MS), involves the inflammation of the optic nerve and the degeneration of retinal ganglion cells (RGCs). Although previous studies suggest that retinal blood flow alterations occur during optic neuritis, the precise location, the degree of impairment, and the underlying mechanisms remain unclear. In this study, we utilized two emerging non-invasive imaging techniques, laser speckle flowgraphy (LSFG) and optical coherence tomography angiography (OCTA), to investigate retinal vascular changes in a mouse model of MS, known as experimental autoimmune encephalomyelitis (EAE). We associated these changes with leukostasis, RGC injury, and the overall progression of EAE. LSFG imaging revealed a progressive reduction in retinal blood flow velocity and increased vascular resistance near the optic nerve head in the EAE model, indicating impaired ocular blood flow. OCTA imaging demonstrated significant decreases in vessel density, number of junctions, and total vessel length in the intermediate and deep capillary plexus of the EAE mice. Furthermore, our analysis of leukostasis revealed a significant increase in adherent leukocytes in the retinal vasculature of the EAE mice, suggesting the occurrence of vascular inflammation in the early development of EAE pathology. The abovechanges preceded or were accompanied by the characteristic hallmarks of optic neuritis, such as RGC loss and reduced visual acuity. Overall, our study sheds light on the intricate relationship between retinal vascular alterations and the progression of optic neuritis as well as MS clinical score. It also highlights the potential for the development of image-based biomarkers for the diagnosis and monitoring of optic neuritis as well as MS, particularly in response to emerging treatments.
Topics: Mice; Animals; Tomography, Optical Coherence; Leukostasis; Optic Neuritis; Encephalomyelitis, Autoimmune, Experimental; Inflammation; Disease Models, Animal; Multiple Sclerosis; Angiography
PubMed: 38067113
DOI: 10.3390/cells12232685 -
Research Square Nov 2023Within the bloodstream, monocytes must traverse the microvasculature to prevent leukostasis, which is the entrapment of monocytes within the confines of the...
Within the bloodstream, monocytes must traverse the microvasculature to prevent leukostasis, which is the entrapment of monocytes within the confines of the microvasculature. Using the model cell line, THP-1, and VCAM-1 coated channels to simulate the microvasculature, we demonstrate that monocytes predominantly adopt an amoeboid phenotype, which is characterized by the formation of blebs. As opposed to cortical actin flow in leader blebs, cell movement is correlated with myosin contraction at the cell rear. Previously, we documented that cofilin-1 promotes cortical actin turnover at leader bleb necks in melanoma cells. In monocytes, our data suggest that cofilin-1 promotes the local upregulation of myosin contractility through actin cytoskeleton remodeling. In support of this concept, cofilin-1 is found to localize to a single cell edge. Moreover, the widespread upregulation of myosin contractility was found to inhibit migration. Thus, monocytes within the microvasculature may avoid entrapment by adopting an amoeboid mode of migration.
PubMed: 37961301
DOI: 10.21203/rs.3.rs-3496552/v1 -
Cureus Sep 2023TP53-mutated (TP53m) acute myeloid leukemia (AML) comprises only 5-15% of de novo AML, associated with poor survival outcomes due to its resistance to conventional...
Rare Ring Chromosome [r(15)]: Cytogenetic Abnormality in TP53-Mutated De Novo AML-M4 Masked as Gastrointestinal Bleed With Rapidly Progressing Hyperleukocytosis and Leukostasis.
TP53-mutated (TP53m) acute myeloid leukemia (AML) comprises only 5-15% of de novo AML, associated with poor survival outcomes due to its resistance to conventional therapy. Ring chromosomes, an even more rare subset of genetic anomalies, occur in only 2% of cases. We report a unique case of de novo AML with both TP53 and ring chromosome anomalies leading to a catastrophic outcome in a 72-year-old male who initially presented with gastrointestinal bleeding (GIB) and urethral stone status post-cystoscopy with J-stent placement. He had no history of chemotherapy use, radiation, benzene exposure, or any other risk factors except for his age. He was noted to have pancytopenia, for which bone marrow biopsy, flow cytometry, and cytogenetic studies were done. Biopsy reported an interesting next-generation sequenced TP53-mutated AML, which correlates with a low rate of response to standard chemotherapy except for bone marrow transplants. Notably, with a complex aberration of 45 XY with multiple translocations (t), deletions (del), inversions (inv), derivative (der) breakpoints, aneuploidy, and rare ring and maker chromosomes, his case was complicated with rapid-onset and very severe hyperleucostasis, reflecting the prognostic value of this rare cytogenetic configuration. The patient expired within 48 hours of diagnosis, despite the urgent initiation of cytoreductive therapy and the mitigation of tumor lysis syndrome with Rasburicase. To the best of our knowledge, this is one of the first AML-M4 patients with rapid-onset leucostasis and the demise of next-generation sequences (NGS) in a de Novo AML patient with this rare complex combination.
PubMed: 37779685
DOI: 10.7759/cureus.46119 -
Journal of Hematology Aug 2023Chronic myelogenous leukemia (CML) is a hematologic malignancy with unique significance to the field of hematology and oncology, specifically due to the development of...
Chronic myelogenous leukemia (CML) is a hematologic malignancy with unique significance to the field of hematology and oncology, specifically due to the development of tyrosine kinase inhibitors (TKIs). CML often presents with nonspecific symptoms, and the quality of life in patients with CML has drastically improved as a result of TKIs. However, complications of CML including the risk of transforming into life-threatening blast crises continue to exist. Further, as most patients are asymptomatic in the chronic phase, patients often present with serious complications associated with noncompliance to TKIs. For example, central nervous system (CNS) manifestations of CML have been reported, both as the initial presentation of undiagnosed CML and as known complication of uncontrolled CML. Hyperleukocytosis is a manifestation of uncontrolled CML and leukostasis is a complication, occurring in cases of acute myeloid leukemia (AML). Here we present a rare case of leukostasis in a patient with known CML presenting on computed tomography (CT) as intracranial masses in the chronic phase. Our goal is to discuss this rare case of leukostasis in adult CML and describe its management.
PubMed: 37692864
DOI: 10.14740/jh1150 -
Annals of Intensive Care Sep 2023Acute respiratory failure (ARF) is the leading cause of intensive care unit (ICU) admission in patients with Acute Myeloid Leukemia (AML) and data on prognostic factors...
Characteristics and outcomes of patients with acute myeloid leukemia admitted to intensive care unit with acute respiratory failure: a post-hoc analysis of a prospective multicenter study.
BACKGROUND
Acute respiratory failure (ARF) is the leading cause of intensive care unit (ICU) admission in patients with Acute Myeloid Leukemia (AML) and data on prognostic factors affecting short-term outcome are needed.
METHODS
This is a post-hoc analysis of a multicenter, international prospective cohort study on immunocompromised patients with ARF admitted to ICU. We evaluated hospital mortality and associated risk factors in patients with AML and ARF; secondly, we aimed to define specific subgroups within our study population through a cluster analysis.
RESULTS
Overall, 201 of 1611 immunocompromised patients with ARF had AML and were included in the analysis. Hospital mortality was 46.8%. Variables independently associated with mortality were ECOG performance status ≥ 2 (OR = 2.79, p = 0.04), cough (OR = 2.94, p = 0.034), use of vasopressors (OR = 2.79, p = 0.044), leukemia-specific pulmonary involvement [namely leukostasis, pulmonary infiltration by blasts or acute lysis pneumopathy (OR = 4.76, p = 0.011)] and liver SOFA score (OR = 1.85, p = 0.014). Focal alveolar chest X-ray pattern was associated with survival (OR = 0.13, p = 0.001). We identified 3 clusters, that we named on the basis of the most frequently clinical, biological and radiological features found in each cluster: a "leukemic cluster", with high-risk AML patients with isolated, milder ARF; a "pulmonary cluster", consisting of symptomatic, highly oxygen-requiring, severe ARF with diffuse radiological findings in heavily immunocompromised patients; a clinical "inflammatory cluster", including patients with multi-organ failures in addition to ARF. When included in the multivariate analysis, cluster 2 and 3 were independently associated with hospital mortality.
CONCLUSIONS
Among AML patients with ARF, factors associated with a worse outcome are related to patient's background (performance status, leukemic pulmonary involvement), symptoms, radiological findings, the need for vasopressors and the liver SOFA score. We identified three specific ARF syndromes in AML patients, which showed a prognostic significance and could guide clinicians to optimize management strategies.
PubMed: 37658994
DOI: 10.1186/s13613-023-01172-3