Cytogenetic abnormalities in patients with hematological malignancies in Lahore city, Pakistan

Hematological and hematopoietic cells malignancies of the genes and hematopoietic cells are associated with the genetic mutation, often at the chromosomal level. The standard cytogenetic study is widely accepted as one of the main diagnostics and prognostic determinants in patients. Therefore, the current descriptive and cross-sectional study sought to determine the cytogenetic analysis of frequent hematological malignancies in Pakistan. A total of 202 peripheral bone marrow or blood samples from patients with benign and malignant hematological malignancy were taken using a conventional G-banding technique. Among enrolled patients, the mean age was 21.5 years ± 23.4, and gender-wise distribution showed a marked predominance of the male 147 (73%) population compared to the female 55 (27%). Patients in the age group (2-10 years) had the highest frequency, 48 (24%), of hematological neoplasms, followed by age (11-20 years) with 40 (20%). Normal karyotypes (46, XX/46, XY) was found in 51% (n=103) patients. Furthermore, the frequency of complex karyotype was 30 (15%), while normal was seen in 171 (85%) patients. Pre-B Acute Lymphoblastic Leukemia (Pre-B ALL) was the most prevalent malignancy of 66 (33%), followed by Chronic Myelogenous Leukemia (CML) of 41 (20%) and Acute Lymphocytic Leukemia of 29 (14%). Translocation was the most prevalent 50 (25%), followed by hypotriploidy 14 (7%) and monosomy 8 (4%) on chromosome aberration analysis. In addition, t(9:22) translocation was found to be 20 (10%) in CML, with the majority in the age group (31-40 years). This study recommends that karyotyping should be tested frequently in hematological conditions because it may provide insight into the relative chromosomal changes associated with particular malignancies.

Apoptotic effect of Bulbine Natalensis and Chlorophytum Comosum in myelogenous Leukemia K562 cell line

Bulbine natalensis and Chorophytum comosum are potential medicinal source for the treatment of cancers. Chronic myeloid leukaemia is a hematopoietic stem cells disorder treated by tyrosine kinase inhibitors but often cause recurrence of the leukaemia after cessation of therapy, hence require alternative treatment. This study determines the anti-cancer effect of leaf, root and bulb methanolic and aqueous extracts of B. natalensis and C. comosum in chronic human myelogenous leukaemia (K562) cell line by MTT, Hoechst bis-benzimide nuclear and annexin V stain assays. The root methanolic extract of B. natalensis and C. comosum showed a high cytotoxicity of 8.6% and 16.7% respectively on the K562 cell line at 1,000 μg/ml concentration. Morphological loss of cell membrane integrity causing degradation of the cell and fragmentation were observed in the root methanolic extract of both plants. A high apoptosis (p < 0.0001) was induced in the K562 cells by both leaf and root extracts of the C. comosum compared to the B. natalensis. This study shows both plants possess apoptotic effect against in vitro myelogenous leukaemia which contributes to the overall anti-cancer properties of B. natalensis and C. comosum to justify future therapeutic applications against chronic myelogenous leukaemia blood cancer.

Indication-Specific Generic Uptake of Imatinib Demonstrates the Impact of Skinny Labeling

PURPOSE Generic competition can be delayed if brand-name manufacturers obtain additional patents on supplemental uses. The US Food and Drug Administration allows generic drug manufacturers to market versions with skinny labels that exclude patent-protected indications. This study assessed whether use of generic versions of imatinib varied between indications included and excluded from the skinny labels. METHODS In this cross-sectional study, we identified adult patients covered by commercial insurance or Medicare Advantage plans who initiated imatinib from February 2016 (first generic availability) to September 2020. Generic versions were introduced with skinny labels that included indications covering treatment of chronic myelogenous leukemia (CML) but excluded treatment of gastrointestinal stromal tumors (GISTs) because of remaining patent protections. Logistic regression was used to determine whether use of generic versus brand-name imatinib differed between patients with a diagnosis of CML or GIST, adjusting for demographics, insurance type, prior use of brand-name drugs, and calendar month. RESULTS Among 2,000 initiators, 934 (47%) had CML and 686 (34%) had GIST. Within 3 years after generics entered the market, more than 90% of initiators in both groups used generic imatinib. Initiation of generic imatinib was slightly lower among patients with GIST than among patients with CML (85% v 88%; adjusted odds ratio 0.56; 95% CI, 0.39 to 0.80; P ≤ .001). CONCLUSION Generic versions of imatinib were dispensed frequently for indications both included (CML) and excluded (GIST) from the skinny labeling, although patients with GIST were slightly less likely to receive a generic version. The skinny labeling pathway allowed generics to enter the market before patent protection for treating patients with GIST expired, facilitating lower drug prices.

Herpes simplex virus-infected squamous cell carcinoma: a case report

Background Herpes simplex virus (HSV)-1 is a highly prevalent, non-oncogenic virus that has higher morbidity in immunocompromised hosts. Its most common clinical manifestation is superficial ulceration of the integument or mucus membranes. Case presentation A 65-year-old woman with a history of acute myelogenous leukemia treated with allogenic peripheral blood stem cell transplant presented for resection of an ulcerated buccal squamous cell carcinoma. We report a case of HSV-1-infected malignant cells discovered on histopathological examination of the carcinoma specimen ultimately treated with valacyclovir. Conclusions HSV-1 is not considered an oncogenic virus itself but may increase risk of malignant progression. Cancer cells are vulnerable to superimposed viral infections, including HSV-1, which likely led to the findings in this case.

Designed Hybrid Anticancer Nuclear Localized Peptide Inhibits Aggressive Cancer Cell Proliferation

A fused peptide containing the nuclear localizing sequence (NLS) has been designed and executed, that greatly affects human chronic myelogenous leukemia (CML) cell proliferation by targeting both the nuclear and...

Vessel Wall Magnetic Resonance Imaging Findings of Bilateral Middle Cerebral Artery Stenosis Associated with Nilotinib

Nilotinib is a Bcr-Abl tyrosine kinase inhibitor used to treat chronic myelogenous leukemia. There have been case reports of nilotinib-related vasculopathy. However, most cases present peripheral artery disease, whilst reports of nilotinib-related cerebrovascular disease are quite uncommon. Herein, we report a case of nilotinib-induced intracranial stenosis in a patient with recurrent transient ischemic attacks and discuss the results of serial vessel wall magnetic resonance imaging.

A modified perfusion protocol for pulmonary endarterectomy in a patient with a hematologic malignancy treated with a tyrosine kinase inhibitor

Tyrosine kinase inhibitors (TKI) are known to be highly effective in the treatment of various cancers with kinase-domain mutations such as chronic myelogenous leukemia. However, they have important side effects such as increased vascular permeability and pulmonary hypertension. In patients undergoing pulmonary endarterectomy with deep hypothermic circulatory arrest, these side effects may exacerbate postoperative complications such as reperfusion edema and persistent pulmonary hypertension. We report on a simple modification of the perfusion strategy to increase intravascular oncotic pressure by retrograde autologous priming and the addition of packed cells and albumin in a patient treated with a TKI.

Semi-Synthesis, Cytotoxic Evaluation, and Structure—Activity Relationships of Brefeldin A Derivatives with Antileukemia Activity

Brefeldin A (1), a potent cytotoxic natural macrolactone, was produced by the marine fungus Penicillium sp. (HS-N-29) from the medicinal mangrove Acanthus ilicifolius. Series of its ester derivatives 2−16 were designed and semi-synthesized, and their structures were characterized by spectroscopic methods. Their cytotoxic activities were evaluated against human chronic myelogenous leukemia K562 cell line in vitro, and the preliminary structure–activity relationships revealed that the hydroxy group played an important role. Moreover, the monoester derivatives exhibited stronger cytotoxic activity than the diester derivatives. Among them, brefeldin A 7-O-2-chloro-4,5-difluorobenzoate (7) exhibited the strongest inhibitory effect on the proliferation of K562 cells with an IC50 value of 0.84 µM. Further evaluations indicated that 7 induced cell cycle arrest, stimulated cell apoptosis, inhibited phosphorylation of BCR-ABL, and thereby inactivated its downstream AKT signaling pathway. The expression of downstream signaling molecules in the AKT pathway, including mTOR and p70S6K, was also attenuated after 7-treatment in a dose-dependent manner. Furthermore, molecular modeling of 7 docked into 1 binding site of an ARF1–GDP-GEF complex represented well-tolerance. Taken together, 7 had the potential to be served as an effective antileukemia agent or lead compound for further exploration.

A Review of Noninfectious Diseases Masquerading as Acute Mastoiditis

Objective Acute mastoiditis is commonly attributed to infection. Rarely do clinicians encounter cases that do not respond to traditional antibiotics or surgical management. The goal of this study was to systematically review the literature to characterize diseases masquerading as acute infectious mastoiditis. Data Sources PubMed, Embase, and Scopus. Review Methods A systematic review was performed to identify all publications that reported on diseases with presentations mimicking acute mastoiditis, defined as postauricular redness, swelling, and tenderness. We included clinical prospective studies, retrospective studies, and case series/reports. Exclusion criteria included non-English articles, letters/commentaries, abstracts, and review articles. Results Out of 3339 results, 35 studies met final inclusion criteria. In children, 11 diseases were reported to mimic mastoiditis, including solid tumors, hematologic diseases, and autoimmune/inflammatory diseases. The most common disease in children was Langerhans cell histiocytosis, followed by rhabdomyosarcoma and acute myelogenous leukemia. In adults, 8 additional diseases were reported. The most common disease in adults was squamous cell carcinoma, followed by nasopharyngeal carcinoma and Langerhans cell histiocytosis. Presenting symptoms are reviewed, as well as characteristic radiographic, laboratory, and intraoperative features that may assist with diagnosis. A diagnostic algorithm for atypical cases of acute mastoiditis is proposed. Conclusion A small but significant group of diseases in children and adults can mimic acute mastoiditis. In such cases, history and examination alone may be insufficient to reach a diagnosis, and further investigation may be necessary. Otolaryngologists should always be mindful of the possibility that noninfectious pathologies may present with a constellation of symptoms similar to mastoiditis.