scholarly journals Diagnosis, Response Assessment and Treatment Outcomes in Acute Myeloid Leukemia (AML)

2021 ◽  
pp. 665-705
Author(s):  
Alireza Heidari ◽  
Ricardo Gobato ◽  
Abhijit Mitra
Keyword(s):  
Bone Marrow ◽  
Cancer Cells ◽  
Blood Cells ◽  
Prolonged Exposure ◽  
Genetic Diseases ◽  
White Blood Cells ◽  
Response Assessment ◽  
Severe Bleeding ◽  
Proliferating Cells ◽  
Assessment And Treatment

Leukemia occurs when a person's entire bone marrow tissue space is occupied by cancer cells or blasts that are young, dysfunctional, undifferentiated, and proliferating cells. In this situation, there is no space left for the bone marrow to be able to produce normal blood cells such as platelets, red and white blood cells. These patients suffer from severe bleeding due to decreased platelets or due to a decrease in white blood cells, which are often diagnosed with dangerous infections that cause death in these patients. The exact cause of leukemias is not yet known, but a number of factors have been identified that play a role in the development of these cancers, including high doses of radiation or atomic radiation, prolonged exposure to certain chemicals, and some Mentioned viruses and some genetic diseases such as Down syndrome or underlying diseases. Keywords: Cancer; Cells; Tissues; Tumors; Prevention; Prognosis; Diagnosis; Imaging; Screening, Treatment; Management

scholarly journals A Comparison of Flow Cytometry, Bone Marrow Biopsy and Bone Marrow Aspirates in the Detection of Lymphoid Infiltration in T Cell Disorders

2021 ◽  
pp. 674-714
Author(s):  
Elena Locci ◽  
Silvia Raymond
Keyword(s):  
Bone Marrow ◽  
Cancer Cells ◽  
Blood Cells ◽  
Prolonged Exposure ◽  
Genetic Diseases ◽  
White Blood Cells ◽  
Severe Bleeding ◽  
Proliferating Cells ◽  
High Doses ◽  
Lymphoid Infiltration

Leukemia occurs when a person's entire bone marrow tissue space is occupied by cancer cells or blasts that are young, dysfunctional, undifferentiated, and proliferating cells. In this situation, there is no space left for the bone marrow to be able to produce normal blood cells such as platelets, red and white blood cells. These patients suffer from severe bleeding due to decreased platelets or due to a decrease in white blood cells, which are often diagnosed with dangerous infections that cause death in these patients. The exact cause of leukemias is not yet known, but a number of factors have been identified that play a role in the development of these cancers, including high doses of radiation or atomic radiation, prolonged exposure to certain chemicals, and some Mentioned viruses and some genetic diseases such as Down syndrome or underlying diseases. Keywords: Cancer; Cells; Tissues, Tumors; Prevention, Prognosis; Diagnosis; Imaging; Screening; Treatment; Management

Segmentation of Leukemia Cells Using Clustering

2019 ◽  
Vol 10 (2) ◽  
pp. 39-48
Author(s):  
Eman Mostafa ◽  
Heba A. Tag El-Dien
Keyword(s):  
Bone Marrow ◽  
Cancer Cells ◽  
Blood Cells ◽  
White Blood Cells ◽  
Leukemia Cells ◽  
Microscopic Image ◽  
Processing Stage ◽  
Clustering Techniques ◽  
Fuzzy C Means

Leukemia is a blood cancer which is defined as an irregular augment of undeveloped white blood cells called “blasts.” It develops in the bone marrow, which is responsible for blood cell generation including leukocytes and white blood cells. The early diagnosis of leukemia greatly helps in the treatment. Accordingly, researchers are interested in developing advanced and accurate automated techniques for localizing such abnormal blood cells. Subsequently, image segmentation becomes an important image processing stage for successful feature extraction and classification of leukemia in further stages. It aims to separate cancer cells by segmenting the microscopic image into background and cancer cells that are known as the region of interested (ROI). In this article, the cancer blood cells were segmented using two separated clustering techniques, namely the K-means and Fuzzy-c-means techniques. Then, the results of these techniques were compared to in terms of different segmentation metrics, such as the Dice, Jac, specificity, sensitivity, and accuracy. The results proved that the k-means provided better performance in leukemia blood cells segmentation as it achieved an accuracy of 99.8% compared to 99.6% with the fuzzy c-means.

Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia

2019 ◽  
Vol 18 (14) ◽  
pp. 1936-1951 ◽  
Author(s):  
Raghav Dogra ◽  
Rohit Bhatia ◽  
Ravi Shankar ◽  
Parveen Bansal ◽  
Ravindra K. Rawal
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Adverse Effects ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
White Blood Cells ◽  
Phase Iii ◽  
Acute Myeloid

Background: Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly known as AG-221 which is being marketed under the name Idhifa to treat R/R AML with IDH2 mutation. The present review depicts the broad profile of enasidenib including various aspects of chemistry, preclinical, clinical studies, pharmacokinetics, mode of action and toxicity studies. Methods: Various reports and research articles have been referred to summarize different aspects related to chemistry and pharmacokinetics of enasidenib. Clinical data was collected from various recently published clinical reports including clinical trial outcomes. Result: The various findings of enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also presented good safety and efficacy profile along with 9.3 months overall survival rates of patients in which disease has relapsed. The drug is still under study either in combination or solely to treat hematological malignancies. Molecular modeling studies revealed that enasidenib binds to its target through hydrophobic interaction and hydrogen bonding inside the binding pocket. Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels, etc. Conclusion: Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. Phase III trial on the Enasidenib is still under process along with another trial to test its potency against other cell lines. Edasidenib is associated with certain adverse effects, which can be reduced by investigators by designing its newer derivatives on the basis of SAR studies. Hence, it may come in the light as a potent lead entity for anticancer treatment in the coming years.

scholarly journals Adult Mice With Targeted Mutation of the Interleukin-11 Receptor (IL11Ra) Display Normal Hematopoiesis

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2148-2159 ◽  
Author(s):  
Harshal H. Nandurkar ◽  
Lorraine Robb ◽  
David Tarlinton ◽  
Louise Barnett ◽  
Frank Köntgen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Bone Marrow Cells ◽  
White Blood Cells ◽  
Null Mutation ◽  
Wild Type ◽  
Normal Numbers ◽  
Interleukin 11 ◽  
Marrow Cells

Abstract Interleukin-11 (IL-11) is a pleiotropic growth factor with a prominent effect on megakaryopoiesis and thrombopoiesis. The receptor for IL-11 is a heterodimer of the signal transduction unit gp130 and a specific receptor component, the α-chain (IL-11Rα). Two genes potentially encode the IL-11Rα: the IL11Ra and IL11Ra2 genes. The IL11Ra gene is widely expressed in hematopoietic and other organs, whereas the IL11Ra2 gene is restricted to only some strains of mice and its expression is confined to testis, lymph node, and thymus. To investigate the essential actions mediated by the IL-11Rα, we have generated mice with a null mutation of IL11Ra (IL11Ra−/−) by gene targeting. Analysis of IL11Ra expression by Northern blot and reverse transcriptase-polymerase chain reaction, as well as the absence of response of IL11Ra−/− bone marrow cells to IL-11 in hematopoietic assays, further confirmed the null mutation. Compensatory expression of the IL11Ra2 in bone marrow cells was not detected. IL11Ra−/− mice were healthy with normal numbers of peripheral blood white blood cells, hematocrit, and platelets. Bone marrow and spleen contained normal numbers of cells of all hematopoietic lineages, including megakaryocytes. Clonal cultures did not identify any perturbation of granulocyte-macrophage (GM), erythroid, or megakaryocyte progenitors. The number of day-12 colony-forming unit-spleen progenitors were similar in wild-type and IL11Ra−/− mice. The kinetics of recovery of peripheral blood white blood cells, platelets, and bone marrow GM progenitors after treatment with 5-flurouracil were the same in IL11Ra−/− and wild-type mice. Acute hemolytic stress was induced by phenylhydrazine and resulted in a 50% decrease in hematocrit. The recovery of hematocrit was comparable in IL11Ra−/− and wild-type mice. These observations indicate that IL-11 receptor signalling is dispensable for adult hematopoiesis.

scholarly journals Detection of Blood Cancer Cells Using Microscopic Images

2021 ◽  
Vol 9 (8) ◽  
pp. 995-1003
Author(s):  
Vidyashree M S
Keyword(s):  
Machine Learning ◽  
Support Vector Machine ◽  
Cancer Cells ◽  
Blood Cells ◽  
White Blood Cells ◽  
Machine Learning Algorithms ◽  
Support Vector ◽  
Support Vector Machine Algorithm ◽  
Blood Cancer ◽  
Acute Myeloid

Abstract: Blood Cancer cells forming a tissue is called lymphoma. Thus, disease decreases the cells to fight against the infection or cancer blood cells. Blood cancer is also categorized in too many types. The two main categories of blood cancer are Acute Lymphocytic Lymphoma and Acute Myeloid Lymphoma. In this project proposes a approach that robotic detects and segments the nucleolus from white blood cells in the microscopic Blood images. Here in this project, we have used the two Machine learning algorithms that are k-means algorithm, Support vector machine algorithm. K-mean algorithm is use for segmentation and clustering. Support vector machine algorithm is used for classification. Keywords: k-means, Support vector machine, Lymphoma, Acute Lymphocytic Lymphoma, Machine Learning

scholarly journals Subchronic Oral Toxicity Study of Decitabine in Combination With Tetrahydrouridine in CD-1 Mice

2014 ◽  
Vol 33 (2) ◽  
pp. 75-85 ◽  
Author(s):  
Pramod Terse ◽  
Kory Engelke ◽  
Kenneth Chan ◽  
Yonghua Ling ◽  
Douglas Sharpnack ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Combination Therapy ◽  
Food Consumption ◽  
Blood Cells ◽  
Recovery Period ◽  
White Blood Cells ◽  
Clinical Pathology ◽  
High Dose ◽  
Severe Toxicity ◽  
Oral Toxicity

Decitabine (5-aza-2′-deoxycytidine; DAC) in combination with tetrahydrouridine (THU) is a potential oral therapy for sickle cell disease and β-thalassemia. A study was conducted in mice to assess safety of this combination therapy using oral gavage of DAC and THU administered 1 hour prior to DAC on 2 consecutive days/week for up to 9 weeks followed by a 28-day recovery to support its clinical trials up to 9-week duration. Tetrahydrouridine, a competitive inhibitor of cytidine deaminase, was used in the combination to improve oral bioavailability of DAC. Doses were 167 mg/kg THU followed by 0, 0.2, 0.4, or 1.0 mg/kg DAC; THU vehicle followed by 1.0 mg/kg DAC; or vehicle alone. End points evaluated were clinical observations, body weights, food consumption, clinical pathology, gross/histopathology, bone marrow micronuclei, and toxicokinetics. There were no treatment-related effects noticed on body weight, food consumption, serum chemistry, or urinalysis parameters. Dose- and gender-dependent changes in plasma DAC levels were observed with a Cmax within 1 hour. At the 1 mg/kg dose tested, THU increased DAC plasma concentration (∼10-fold) as compared to DAC alone. Severe toxicity occurred in females receiving high-dose 1 mg/kg DAC + THU, requiring treatment discontinuation at week 5. Severity and incidence of microscopic findings increased in a dose-dependent fashion; findings included bone marrow hypocellularity (with corresponding hematologic changes and decreases in white blood cells, red blood cells, hemoglobin, hematocrit, reticulocytes, neutrophils, and lymphocytes), thymic/lymphoid depletion, intestinal epithelial apoptosis, and testicular degeneration. Bone marrow micronucleus analysis confirmed bone marrow cytotoxicity, suppression of erythropoiesis, and genotoxicity. Following the recovery period, a complete or trend toward resolution of these effects was observed. In conclusion, the combination therapy resulted in an increased sensitivity to DAC toxicity correlating with DAC plasma levels, and females are more sensitive compared to their male counterparts.

scholarly journals Quantification and three-dimensional microanatomical organization of the bone marrow

2017 ◽  
Vol 1 (6) ◽  
pp. 407-416 ◽  
Author(s):  
Cesar Nombela-Arrieta ◽  
Markus G. Manz
Keyword(s):  
Bone Marrow ◽  
Blood Cells ◽  
Structural Organization ◽  
Imaging Techniques ◽  
White Blood Cells ◽  
Three Dimensional ◽  
The Body ◽  
Cellular Composition ◽  
Spatial Logic ◽  
Health And Disease

Abstract Bone marrow (BM) constitutes one of the largest organs in mice and humans, continuously generating, in a highly regulated manner, red blood cells, platelets, and white blood cells that together form the majority of cells of the body. In this review, we provide a quantitative overview of BM cellular composition, we summarize emerging knowledge on its structural organization and cellular niches, and we argue for the need of multidimensional approaches such as recently developed imaging techniques to uncover the complex spatial logic that underlies BM function in health and disease.

scholarly journals Megaloblastosis Produced by a Cytosine Antagonist

Blood ◽  
1963 ◽  
Vol 21 (3) ◽  
pp. 352-362 ◽  
Author(s):  
R. W. TALLEY ◽  
V. K. VAITKEVICIUS
Keyword(s):  
Bone Marrow ◽  
Dna Synthesis ◽  
Mechanism Of Action ◽  
Cytosine Arabinoside ◽  
Peripheral Blood ◽  
Blood Cells ◽  
White Blood Cells ◽  
Structural Similarity ◽  
Mitotic Abnormalities ◽  
Temporary Decrease

Abstract 1. Cytosine arabinoside induced objective, but temporary, decrease of tumor masses in three patients with lymphosarcoma and slight decrease in some lesions in two out of ten treated patients with disseminated carcinomatosis. 2. In doses of 3 to 50 mg./Kg. given at varying intervals, cytosine arabinoside induced definite megaloblastic changes in the marrow of all patients studied. Mitotic abnormalities similar to those found in other megaloblastic anemias also occurred. 3. Associated with bone marrow changes, depressions of hemoglobin, white blood cells and platelets in the peripheral blood were observed. 4. The exact mechanism of action of cytosine arabinoside has not been elucidated. It is speculated that because of the close structural similarity between cytidylic acid, cytosine arabinoside could interfere with DNA synthesis.

scholarly journals A review of the treatment landscape in paroxysmal nocturnal haemoglobinuria: where are we now and where are we going?

2020 ◽  
Vol 1 ◽  
pp. 263300402095934
Author(s):  
Morag Griffin ◽  
Richard Kelly ◽  
Alexandra Pike
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Life Expectancy ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Treatment Options ◽  
White Blood Cells ◽  
Paroxysmal Nocturnal Haemoglobinuria ◽  
Complement Cascade ◽  
Future Treatments

Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-orphan disease, which until 15 years ago had limited treatment options. Eculizumab, a monoclonal antibody that inhibits C5 in the terminal complement cascade, has revolutionised treatment for this disease, near normalising life expectancy and improving quality of life for patients. The treatment landscape of PNH is now evolving, with ravulizumab a second longer acting intravenous C5 inhibitor now licenced by the FDA and EMA. With different therapeutic targets in the complement cascade and difference modalities of treatment, including subcutaneous, oral and intravenous therapies being developed, increasing independence for patients and reducing healthcare requirements. This review discusses the current and future therapies for PNH. Lay summary Review of current and future treatments for patients with Paroxysmal Nocturnal Haemoglobinuria What is Paroxysmal Nocturnal Haemoglobinuria? Paroxysmal nocturnal haemoglobinuria (PNH) is a very rare disease. It arises from PNH stem cells in the bone marrow. In a normal bone marrow these are inactive; however, if there has been a problem in the bone marrow, the PNH stem cells can expand and make PNH red blood cells, white blood cells and platelets. The problem with these cells is that they lack the cell surface markers that usually protect them. Red blood cells are broken down in the circulation rather than the spleen, which gives rise to PNH symptoms such as abdominal pain, difficulty swallowing, erectile dysfunction and red or black urine (known as haemoglobinuria). The white blood cells and platelets are ‘stickier’ increasing the risk of blood clots. Previously life expectancy was reduced as there were limited treatment options available. What was the aim of this review? To provide an overview of current and future treatment options for PNH Which treatments are available? • Eculizumab is an treatment given through a vein (intravenous) every week for 5 weeks then every 2 weeks after this, and has been available for 13 years, improving life expectancy to near normal. • Ravulizumab is a newer intravenous treatment similar to eculizumab but is given every 8 weeks instead of every 2 weeks. In clinical studies it was comparable with eculizumab. • Future Treatments - There is new research looking at different methods of treatment delivery, including injections under the skin (subcutaneous) that patients can give themselves, treatments taken by mouth (oral) or a combination of an intravenous and oral treatment for those patients who are not optimally controlled on eculizumab or ravulizumab. What does this mean? PNH is now treatable. For years, the only drug available was eculizumab, but now different targets and drug trials are available. Ravulizumab is currently the only second licenced product available, in USA and Europe, there are other medications active in clinical trials. Why is this important? The benefit for patients, from treatment every 2 weeks to every 8 weeks is likely to be improved further with the development of these new treatments, providing patients with improved disease control and independence. As we move into an era of more patient-friendly treatment options, the PNH community both physicians and patients look forward to new developments as discussed in this article.

Relationships between plasma adiponectin and blood cells, hepatopancreatic enzymes in women

2004 ◽  
Vol 91 (02) ◽  
pp. 360-366 ◽  
Author(s):  
Katsuhiko Namioka ◽  
Shinji Katayose ◽  
Miyao Matsubara
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Bone Marrow ◽  
Blood Cells ◽  
White Blood Cells ◽  
Serum Triglyceride ◽  
Plasma Adiponectin ◽  
The Metabolic Syndrome ◽  
Before And After ◽  
Bone Marrow Function

SummaryAdiponectin, which is secreted specifically from adipocyte, is thought to play a key role in the metabolic syndrome. We studied the associations of plasma adiponectin concentrations with blood cells and hepatopancreatic enzymes in 339 women aged 54.0 ± 0.8 (mean ± SE) years. Plasma adiponectin before and after adjustment for body composition or calculated insulin resistance increased in slight anemic women (372.6 ± 2.6 ×104/mm3) compared with non-anemic subjects (471.1 ± 1.7) (all p < 0.0001), and were inversely associated with red blood cells (RBC), hemoglobin, hematocrit, white blood cells and platelet values (p < 0.0001 ∼ 0.02), independent of age, diastolic blood pressure, body mass index, serum triglyceride, insulin resistance or blood urea nitrogen. Age and adiponectin/body fat mass (%) were negative, and blood pressure and insulin resistance were positive significant independent determinants of RBC in stepwise regression analysis. Moreover, adiponectin before and after adjustment were inversely associated with serum ALAT,γGTP and ChE, and positively with amylase levels (p < 0.0001 ∼ 0.02). These results indicate the possibility that increased adiponectin may contribute to the suppressive bone marrow function in vivo. Combined with the leptin’s data, adipocyte derived proteins were related to the hematopoiesis, therefore it has shown the possible existence of adipose tissue/ bone marrow function linkage more clearly. Furthermore, hepatopancreatic enzyme associations with this protein may indicate the possibility that adiponectin will regulate the hepatopancreatic function in health and disease.

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