scholarly journals Organic Nanoparticles as Drug Delivery Systems and Their Potential Role in the Treatment of Chronic Myeloid Leukemia

2019 ◽  
Vol 18 ◽  
pp. 153303381987990 ◽  
Author(s):  
Mohammed Hussein Kamareddine ◽  
Youssef Ghosn ◽  
Antonios Tawk ◽  
Carlos Elia ◽  
Walid Alam ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Chronic Myeloid Leukemia ◽  
Fusion Protein ◽  
Myeloid Leukemia ◽  
Drug Delivery Systems ◽  
Philadelphia Chromosome ◽  
Myeloproliferative Neoplasm ◽  
Delivery Systems ◽  
Treatment Modalities ◽  
Organic Nanoparticles

Chronic myeloid leukemia is a myeloproliferative neoplasm that occurs more prominently in the older population, with a peak incidence at ages 45 to 85 years and a median age at diagnosis of 65 years. This disease comprises roughly 15% of all leukemias in adults. It is a clonal stem cell disorder of myeloid cells characterized by the presence of t(9;22) chromosomal translocation, also known as the Philadelphia chromosome, or its byproducts BCR-ABL fusion protein/messenger RNA, leading to the expression of a protein with enhanced tyrosine kinase activity. This fusion protein has become the main therapeutic target in chronic myeloid leukemia therapy, with imatinib displaying superior antileukemic effects, placing it at the forefront of current treatment protocols and displaying great efficacy. Alternatively, nanomedicine and employing nanoparticles as drug delivery systems may represent new approaches in future anticancer therapy. This review focuses primarily on the use of organic nanoparticles aimed at chronic myeloid leukemia therapy in both in vitro and in vivo settings, by going through a thorough survey of published literature. After a brief introduction on the pathogenesis of chronic myeloid leukemia, a description of conventional, first- and second-line, treatment modalities of chronic myeloid leukemia is presented. Finally, some of the general applications of nanostrategies in medicine are presented, with a detailed focus on organic nanocarriers and their constituents used in chronic myeloid leukemia treatment from the literature.

Biocompatible Nanovesicular Drug Delivery Systems with Targeting Potential for Autoimmune Diseases

2020 ◽  
Vol 26 (42) ◽  
pp. 5488-5502 ◽  
Author(s):  
Yub Raj Neupane ◽  
Asiya Mahtab ◽  
Lubna Siddiqui ◽  
Archu Singh ◽  
Namrata Gautam ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Drug Delivery Systems ◽  
Drug Carriers ◽  
Immunological Tolerance ◽  
Delivery Systems ◽  
The Body ◽  
Autoimmune Response ◽  
Treatment Modalities

Autoimmune diseases are collectively addressed as chronic conditions initiated by the loss of one’s immunological tolerance, where the body treats its own cells as foreigners or self-antigens. These hay-wired antibodies or immunologically capable cells lead to a variety of disorders like rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis and recently included neurodegenerative diseases like Alzheimer’s, Parkinsonism and testicular cancer triggered T-cells induced autoimmune response in testes and brain. Conventional treatments for autoimmune diseases possess several downsides due to unfavourable pharmacokinetic behaviour of drug, reflected by low bioavailability, rapid clearance, offsite toxicity, restricted targeting ability and poor therapeutic outcomes. Novel nanovesicular drug delivery systems including liposomes, niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes and biologically originated exosomes have proved to possess alluring prospects in supporting the combat against autoimmune diseases. These nanovesicles have revitalized available treatment modalities as they are biocompatible, biodegradable, less immunogenic and capable of carrying high drug payloads to deliver both hydrophilic as well as lipophilic drugs to specific sites via passive or active targeting. Due to their unique surface chemistry, they can be decorated with physiological or synthetic ligands to target specific receptors overexpressed in different autoimmune diseases and can even cross the blood-brain barrier. This review presents exhaustive yet concise information on the potential of various nanovesicular systems as drug carriers in improving the overall therapeutic efficiency of the dosage regimen for various autoimmune diseases. The role of endogenous exosomes as biomarkers in the diagnosis and prognosis of autoimmune diseases along with monitoring progress of treatment will also be highlighted.

scholarly journals Atypical Chronic Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5455-5455
Author(s):  
Chandralekha Ashangari ◽  
Praveen K. Tumula
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Philadelphia Chromosome ◽  
Myeloproliferative Neoplasm ◽  
Peripheral Blood Flow ◽  
Current Standard ◽  
Atypical Chronic Myeloid Leukemia ◽  
Wbc Count

Abstract Introduction: Atypical chronic myeloid leukemia (aCML), BCR-ABL1 negative is a rare myelodysplastic syndromes (MDS)/myeloproliferative neoplasm (MPN) for which no current standard of care exists. We present one of the rare presentations of aCML in an elderly patient. Case: A 76 year old male presented to the Hematology clinic for consultation after discharge from local hospital for elevated WBC count. Past medical history was significant for COPD, acid reflux, peripheral arterial disease and hypertension. Physical exam was unremarkable. Initial labs were significant for leukocytosis of 30 k/cu mm, anemia with Hb 10 gm/dl, thrombocytosis 695,000 with neutrophilia of ANC 25,200. Peripheral blood was negative for JAK2 V617F and BCR-ABL. Peripheral blood flow cytometry showed granulocytic left shift with 1.5% myeloblasts. Bone marrow biopsy suggestive of hypercellular marrow (100%) with myeloid predominance, atypical megakaryocytes, increased ring sideroblasts (49% of NRBC), increased blasts (5%) and dysgranulopoeisis over all suggestive of Myelodyplastic Syndrome/Chronic Myeloproliferative Disorder (MDS/MPD). Cytogenetics were positive for U2AF1 positive, CSF3R T6181, CSF3R Q776 pathognomonicof atypical CML and negative for BCR-ABL, FLT3. He was considered transplant ineligible. He was started on Azacitadine and is currently receiving 2nd cycle therapy. He is also receiving darbepoeitin periodically to avoid frequent transfusions. He is currently transfusion independent. Discussion: Increased WBC count (e.g., cutoffs of >40×109/L or 50×109/L), increased percentage of peripheral blood myeloid precursors, female sex, and older age are adverse prognostic factors for overall survival or leukemia-free survival in aCML. aCML cases lack in Philadelphia chromosome. Overall 50-65% of patients show cytogenetic abnormalities. The most frequent is +8 (25%). Other changes such as -7 and del(12p) have also been recurrently observed. Patients with aCML have an estimated median survival between 14 and 30 months. aCML tends to exhibit a more aggressive clinical course than other MDS/MPN subtypes. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Nursing Care Management of Chronic Myeloid Leukemia – A Case Report

2021 ◽  
Vol 10 (16) ◽  
pp. 1182-1184
Author(s):  
Shakib Hasan Sheikh ◽  
Vaishali Tembhare ◽  
Seema Singh ◽  
Savita Pohekar ◽  
Samruddhi Gujar
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Normal Cell ◽  
Care Management ◽  
Fusion Gene ◽  
Philadelphia Chromosome ◽  
Myeloproliferative Neoplasm ◽  
Lymphocytic Leukemia ◽  
Ph Chromosome ◽  
Normal Cell Cycle

Excessive growth of mature granulocytes in the bone marrow induces chronic myeloid leukemia. The excess neoplastic granulocytes travel massively into the peripheral blood and in the end invade the liver and spleen. The protein encoded on the Philadelphia chromosome by the newly created BCR-ABL gene interferes with normal cell cycle activities, including regulating cell proliferation. Philadelphia chromosome is present in 90 - 95 percent of chronic myeloid leukemia (CML) patients. Their involvement is often a vital indicator of persistent disease or posttreatment relapse. However, for the diagnosis of CML, the presence of the Philadelphia chromosome is not specific since it is also present in acute lymphocytic leukemia (ALL) and rarely in acute myeloid leukemia (AML). 1 Chronic myeloid leukemia is a myeloproliferative neoplasm (MPN) characterised by involvement of the fusion gene BCRABL1 located in the Philadelphia chromosome. In reactive neutrophilia or chronic neutrophilic leukemia, the Ph chromosome is pathognomonic to CML and is never registered.2,3

scholarly journals Successful maternal and fetal outcome in a patient with chronic myeloid leukemia on chemotherapy

2020 ◽  
Vol 9 (2) ◽  
pp. 832
Author(s):  
Nishtha Jaiswal ◽  
Harsha Khullar ◽  
Geeta Mediratta ◽  
Sharmistha Garg
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Myeloproliferative Neoplasm ◽  
Case Series ◽  
Fetal Outcome ◽  
Total Leucocyte Count ◽  
Term Survival ◽  
Drug Of Choice ◽  
In Pregnancy

Chronic myeloid leukemia (CML) is a myeloproliferative-neoplasm accounting for 15% of adult leukemias. Management of leukemia in pregnancy and effect of anti-neoplastic agents on pregnancy outcomes is not well investigated. Management of pregnancy in CML is complicated by the fact that drug used in its treatment i.e. imatinib can lead to teratogenicity in fetus, whereas withholding the drug may lead to relapse of disease. However, pregnancy itself does not alter course of CML. A 19-year-old female, was diagnosed with CML at 15 years of age. She was positive for Philadelphia chromosome. She was on imatinib and had achieved clinical, hematologic and molecular remission. Patient was on regular follow-up till 18 years of age. 45 months post diagnosis she presented with 8 weeks amenorrhoea. Ultrasound (USG) done at 5 weeks gestation showed a single live intrauterine fetus. She took imatinib during this period of organogenesis, so she was advised medical termination of pregnancy (MTP) by treating oncologist. However, patient denied MTP, so her imatinib was stopped and pregnancy continued. The quantitative Bcr/Abl PCR transcript levels at 16, 20 and 28 weeks of gestation were not detectable. The patient did not develop any symptoms or signs suggestive of CML and total leucocyte count remained normal throughout pregnancy. Patient went into preterm-labor at 36 weeks gestation and delivered a healthy male baby weighing 3.1 kg. The baby was well and had a normal examination. USG abdomen of baby was also normal. CML in pregnancy is rare and imatinib is the drug of choice with which long term survival is possible. Imatinib in large case series has been known to be associated with adverse fetal outcomes although evidence to the contrary also exists. Further studies are needed to draw a conclusion on this debatable issue.

scholarly journals Genetic Screening for Potential New Targets in Chronic Myeloid Leukemia Based on Drosophila Transgenic for Human BCR-ABL1

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 293
Author(s):  
Marco Lo Iacono ◽  
Elisabetta Signorino ◽  
Jessica Petiti ◽  
Monica Pradotto ◽  
Chiara Calabrese ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Genetic Screening ◽  
Myeloid Leukemia ◽  
Molecular Mechanisms ◽  
Disease Onset ◽  
Philadelphia Chromosome ◽  
Myeloproliferative Neoplasm ◽  
Transforming Activity ◽  
Tight Connection ◽  
First Time

Chronic myeloid leukemia is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome that originates from the reciprocal translocation t(9;22)(q34;q11.2) and encodes for the constitutively active tyrosine kinase protein BCR-ABL1 from the Breakpoint Cluster Region (BCR) sequence and the Abelson (ABL1) gene. Despite BCR-ABL1 being one of the most studied oncogenic proteins, some molecular mechanisms remain enigmatic, and several of the proteins, acting either as positive or negative BCR-ABL1 regulators, are still unknown. The Drosophila melanogaster represents a powerful tool for genetic investigations and a promising model to study the BCR-ABL1 signaling pathway. To identify new components involved in BCR-ABL1 transforming activity, we conducted an extensive genetic screening using different Drosophila mutant strains carrying specific small deletions within the chromosomes 2 and 3 and the gmrGal4,UAS-BCR-ABL1 4M/TM3 transgenic Drosophila as the background. From the screening, we identified several putative candidate genes that may be involved either in sustaining chronic myeloid leukemia (CML) or in its progression. We also identified, for the first time, a tight connection between the BCR-ABL1 protein and Rab family members, and this correlation was also validated in CML patients. In conclusion, our data identified many genes that, by interacting with BCR-ABL1, regulate several important biological pathways and could promote disease onset and progression.

scholarly journals A Case Report of BCR-ABL-JAK2-Positive Chronic Myeloid Leukemia with Complete Hematological and Major Molecular Response to Dasatinib

2021 ◽  
Vol 14 (1) ◽  
pp. 690-694
Author(s):  
Elrazi Awadelkarim Hamid Ali ◽  
Susanna Al-Akiki ◽  
Mohamed A. Yassin
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Myeloproliferative Neoplasm ◽  
Chromosomal Translocation ◽  
Cytogenetic Response ◽  
Response To Treatment ◽  
Medical Illness ◽  
Molecular Response ◽  
Hernial Repair

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm (MPN) that harbors the Philadelphia chromosomal translocation resulting in the uncontrolled production of mature granulocytes. Commonly, patients are diagnosed with CML during blood work for other reasons or enlarged spleen. The diagnosis is based on WHO criteria that require the demonstration of Philadelphia chromosome. Typically, <i>JAK2</i> mutation is not found in <i>BCR-ABL1</i>-positive MPN (CML). Most patients with CML are <i>JAK2</i> negative. It is rare for CML Philadelphia-positive patients to have a coexisting <i>JAK2</i> mutation. Little is known regarding the effect of <i>JAK2</i> mutation on the disease course of CML, the complications, and the response to treatment. We report the case of a 57-year-old man with no previous medical illness who presented with elevated white blood cell count on perioperative assessment for hernial repair; on further workup, he was diagnosed with Philadelphia-positive CML. He was found to have <i>JAK2</i> mutation and was started on treatment with dasatinib and achieved hematological and cytogenetic remission with loss of the <i>JAK2</i> mutation. Patients with <i>JAK2</i>-positive <i>BCR-ABL</i>-positive CML had a good hematological and cytogenetic response to dasatinib. In such rare coexistence of <i>JAK</i> and <i>BCR-ABL</i>, dasatinib is a good option due to multi-kinase activity.

Oxidative Stress and BCR-ABL1 Transcript Levels in Chronic Myeloid Leukemia: an Intricate Relationship

2019 ◽  
Vol 70 (9) ◽  
pp. 3193-3196 ◽  
Author(s):  
Emilia Georgiana Pascu ◽  
Mihnea Alexandru Gaman ◽  
Cornel Moisa ◽  
Amelia Maria Gaman
Keyword(s):  
Oxidative Stress ◽  
Chronic Myeloid Leukemia ◽  
Disease Progression ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Philadelphia Chromosome ◽  
Myeloproliferative Neoplasm ◽  
Compensatory Mechanism ◽  
Stress Levels ◽  
Tki Treatment

Chronic myeloid leukemia (CML) is a chronic myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome. Oxidative stress is involved in CML etiopathogenesis and disease progression, as well as the response to tyrosine kinase inhibitors (TKI) treatment. We evaluated oxidative stress levels in 47 CML patients vs. controls. The total antioxidant capacity (TAC) was measured using a FLUOstar Omega microplate reader (reagents from Sigma-Aldrich). Cellular reactive oxygen species (ROS) were evaluated using a CyFlow SPACE Sysmex flow-cytometer (reagents from Abcam). Oxidative stress levels were higher in CML patients vs. controls. The maximum TAC value and the minimum ROS value were recorded in CML patients with a BCR-ABL1 transcript value of 0.1-1%, suggesting that the production of plasma antioxidants progressively increases as a compensatory mechanism in CML patients undergoing TKI treatment in order to annihilate ROS. The pseudonormalization of the cell redox status observed in these patients could be an alarm signal prior to the development of resistance to TKI treatment or disease progression.

scholarly journals Outgrowth of a CSF3R-mutant clone drives a second myeloproliferative neoplasm in a chronic myeloid leukemia patient: a case report

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sarah A. Carratt ◽  
Diana Brewer ◽  
Julia E. Maxson ◽  
Brian J. Druker ◽  
Theodore P. Braun
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Complex Disease ◽  
Selective Pressure ◽  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Myeloproliferative Neoplasm ◽  
Hematologic Toxicity ◽  
Mutant Clone

Abstract Background Chronic myeloid leukemia (CML) and chronic neutrophilic leukemia (CNL) are two myeloproliferative neoplasms with mutually exclusive diagnostic criteria. A hallmark of CML is the Philadelphia chromosome (Ph), which results in a BCR-ABL1 fusion gene and constitutive tyrosine kinase activity. CNL is a Ph-negative neoplasm and is defined in part by the presence of CSF3R mutations, which drive constative JAK/STAT signaling. Case presentation Here, we report the exceedingly rare co-occurrence of two granulocytic myeloproliferative neoplasms in a 69-year old male patient. After an initial diagnosis of chronic myeloid leukemia, the patient’s clinical course was shaped by hematologic toxicity, the emergence of treatment-resistant BCR-ABL1 clones, and the expansion of a CSF3R-mutant clone without ABL1 mutations under selective pressure from tyrosine kinase inhibitors. The emergence of the CSF3R-mutant, neutrophilic clone led to the diagnosis of CNL as a second myeloproliferative neoplasm in the same patient. Conclusions This is the first reported case of CNL arising subsequent to CML, which occurred under selective pressure from targeted therapy in a patient with complex clonal architecture. Patients with such molecularly complex disease may ultimately benefit from combination therapy that targets multiple oncogenic pathways.

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