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Bioorg Med Chem 2022 Jun 20;69:116894. Epub 2022 Jun 20.

Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates; Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address:

The design, synthesis, and biological activities of a new series of pyrazole derivatives are reported. The target compounds 1a-1w were initially investigated against NCI-60 cancer cell lines. Compounds 1f, 1h, 1k, and 1v exerted the highest anti-proliferative activity over the studied panel of cancer cell lines. Read More

Int J Surg Case Rep 2022 Jun 16;96:107315. Epub 2022 Jun 16.

Department of General Surgery, Mohammed VI University Hospital, Faculty of Medicine and Pharmacy, Laboratory of Anatomy, Microsurgery and Surgery, Experimental and Medical Simulation (LAMCESM), Mohammed Ist University, Oujda, Morocco.

Introduction: Spleen Spontaneous Rupture SRS is a rare phenomenon in which the spleen ruptures without associated trauma. This pathology is rarely caused by Chronic Lymphocytic Leukemia.

Presentation Of The Case: We present a case of a 59-year-old male patient with chronic Lymphocytic Leukemia, who was admitted with an acute abdomen whose clinical and paraclinical examinations revealed a spleen spontaneous rupture. Read More

Eur J Med Chem 2022 Jun 23;239:114559. Epub 2022 Jun 23.

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo nám. 2, 166 10, Prague 6, Czech Republic. Electronic address:

A series of novel 7-aryl-7-deazaadenine-based N-branched acyclic nucleoside phosphonates (aza-ANPs) has been prepared using the optimized Suzuki cross-coupling reaction as the key synthetic step. The final free phosphonates 15a-h were inactive, due to their inefficient transport across cell membranes, but they inhibited Trypanosoma brucei adenine phosphoribosyltransferase (TbrAPRT1) with K values of 1.7-14. Read More

Acta Biochim Pol 2022 Jun 28. Epub 2022 Jun 28.

Department of Hematology, Ganzhou People's Hospital, Ganzhou, China.

Objective: To investigate the cytotoxic effect of polysaccharides derived from Ganoderma lucidum on T lymphocyte leukemia cells.

Methods: Water-soluble polysaccharides were extracted from the fruit bodies of G. lucidum, purified, and characterized using HPGPC-MALLS and NMR. Read More

Cancer Res 2022 May 31. Epub 2022 May 31.

Stanford University, Stanford University, CA, United States.

Small molecule Tyrosine Kinase Inhibitors (TKIs) have revolutionized cancer treatment and greatly improved patient survival. However, life-threatening cardiotoxicity of many TKIs has become a major concern. Ponatinib (ICLUSIG) was developed as an inhibitor of the BCR-ABL oncogene and is among the most cardiotoxic of TKIs. Read More

J Wildl Dis 2022 Jun 28. Epub 2022 Jun 28.

Cavanilles Institute for Biodiversity and Evolutionary Biology, Universidad de Valencia, 46980, Paterna, Spain.

This retrospective study provides an analysis of the prevalence and detectability of canine distemper virus (CDV), feline leukemia virus (FeLV), and feline immunodeficiency virus (FIV) in ocelots (Leopardus pardalis) sheltered in a wild animal recovery center in Guayaquil, Ecuador. Blood samples of 19 rescued ocelots from 2019-20 were analyzed using FeLV p27 antigen enzyme-linked immunosorbent assays (ELISA) and commercial insulated isothermal reverse transcriptase PCR (iiRT-PCR) kits. Using this PCR we detected positive results for CDV (4/17; 23. Read More

J Clin Invest 2022 Jun 28. Epub 2022 Jun 28.

Department of Medical Oncology, Dana Farber Cancer Institute, Boston, United States of America.

Targeted protein degradation is a rapidly advancing and expanding therapeutic approach. Drugs that degrade GSPT1 via the CRL4CRBN ubiquitin ligase are a new class of cancer therapy in active clinical development with evidence of activity against acute myeloid leukemia in early phase trials. However, other than activation of the integrated stress response, the downstream effects of GSPT1 degradation leading to cell death are largely undefined, and no murine models are available to study these agents. Read More

OMICS 2022 Jun 28. Epub 2022 Jun 28.

Department of Nutrition and Dietetics, School of Health Sciences, Nişantaşı University, Istanbul, Turkey.

Acute myeloid leukemia (AML) is a common, complex, and multifactorial malignancy of the hematopoietic system. AML diagnosis and treatment outcomes display marked heterogeneity and patient-to-patient variations. To date, AML-related biomarker discovery research has employed single omics inquiries. Read More

Mol Biol Rep 2022 Jun 28. Epub 2022 Jun 28.

The School of Life Science and Biotechnology, Dalian University, Dalian, 116622, People's Republic of China.

Background: Hyperthermia induces cancer cell death. However, the cytotoxic effect of hyperthermia is not sufficient. Cordycepin can also induce apoptosis in cancer cells and enhance the antitumoral activity of irradiation. Read More

Protein Sci 2022 Jul;31(7):e4354

Department of Chemistry and Biomedical Sciences, Linnaeus University, Kalmar, Sweden.

Diseases with readily available therapies may eventually prevail against the specific treatment by the acquisition of resistance. The constitutively active Abl1 tyrosine kinase known to cause chronic myeloid leukemia is an example, where patients may experience relapse after small inhibitor drug treatment. Mutations in the Abl1 tyrosine kinase domain (Abl1-KD) are a critical source of resistance and their emergence depends on the conformational states that have been observed experimentally: the inactive state, the active state, and the intermediate inactive state that resembles Src kinase. Read More

Panminerva Med 2022 Jun 28. Epub 2022 Jun 28.

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Exp Hematol Oncol 2022 Jun 27;11(1):39. Epub 2022 Jun 27.

Department of Hematology, Shandong Provincial Hospital, Shandong University, No. 324, Jingwu Road, Jinan, 250021, Shandong, China.

Metabolic reprogramming, fundamentally pivotal in carcinogenesis and progression of cancer, is considered as a promising therapeutic target against tumors. In chronic lymphocytic leukemia (CLL) cells, metabolic abnormalities mediate alternations in proliferation and survival compared with normal B cells. However, the role of metabolic reprogramming is still under investigation in CLL. Read More

J Transl Med 2022 Jun 27;20(1):288. Epub 2022 Jun 27.

Department of Hematology, the First Affiliated Hospital of Zhengzhou University, Erqi District, No. 1, Eastern Jianshe Road, Zhengzhou, 450052, Henan, People's Republic of China.

Background: Chemoresistance serves as a huge obstacle for acute myeloid leukemia (AML) patients. To counteract the chemoresistance in AML cells, we discussed the role of maternally expressed gene 3 (MEG3) in arabinocytosine (AraC) chemoresistance in AML cells.

Methods: MEG3, microRNA (miR)-493-5p, methyltransferase-like 3 (METTL3) and MYC expression in AML cells was determined and then their interactions were also analyzed. Read More

Leukemia 2022 Jun 27. Epub 2022 Jun 27.

Section of Hematology, Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA.

Leukemia 2022 Jun 27. Epub 2022 Jun 27.

Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.

Myeloperoxidase (MPO) gene alterations with variable clinical penetrance have been found in hereditary MPO deficiency, but their leukemia association in patients and carriers has not been established. Germline MPO alterations were found to be significantly enriched in myeloid neoplasms: 28 pathogenic/likely pathogenic variants were identified in 100 patients. The most common alterations were c. Read More

Nat Commun 2022 Jun 27;13(1):3679. Epub 2022 Jun 27.

Children's Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, PR China.

Activating FLT3 mutations are the most common mutations in acute myeloid leukemia (AML), but the optimal threshold of FLT3/ITD allelic ratio (AR) among pediatric AML patients remains controversial. Here, we present the outcome and prognostic significance of FLT3/ITD AR analysis among pediatric patients with AML from the TARGET dataset. Applying fitting curve models and threshold effect analysis using the restrictive cubic spline function following Cox proportional hazards models identifies the cut-off value of 0. Read More

Cancer Chemother Pharmacol 2022 Jun 27. Epub 2022 Jun 27.

Department of Pediatrics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

Realgar-Indigo naturalis formula (RIF) is a traditional Chinese medicine containing AsS and effective in treating acute promyelocytic leukemia (APL). The dose of RIF remains to be determined in pediatric patients. Comparison of plasma arsenic concentrations and toxicity between RIF and arsenic trioxide (ATO) treatment in APL may help to establish an appropriate therapeutic dose of RIF for children. Read More

Clin Lymphoma Myeloma Leuk 2022 Jun 5. Epub 2022 Jun 5.

Division of Malignant Hematology, Moffitt Cancer Center, Tampa, FL. Electronic address:

Background: CPX-351 was approved by the FDA in 2017 as frontline induction chemotherapy for patients aged ≥18 years with newly diagnosed acute myeloid leukemia (AML) which includes myelodysplasia-related changes (AML-MRC) and therapy-related acute myeloid leukemia (t-AML). The efficacy of CPX-351 among younger patients (aged <60 years) is currently unclear, as the large, randomized phase 3 study that led to approval of CPX-351 only included patients between the ages of 60 and 75 years.

Methods: We performed a retrospective study of clinical and molecular data from adult patients with newly diagnosed AML-MRC or t-AML treated with CPX-351. Read More

Cesk Slov Oftalmol 2022 ;78(3):144-148

Introduction: Ozurdex® (Allergan Pharmaceuticals, Castlebar Road, Westport, Ireland) is an intravitreal implant containing 0.7 mg of dexamethasone. It is indicated in adult patients for the treatment of diabetic macular edema, cystoid macular edema due to central retinal vein occlusion, and in patients with non-infectious uveitis. Read More

Biochem Biophys Res Commun 2022 Jun 11;619:137-143. Epub 2022 Jun 11.

Institute of Integrated Medicine, Binzhou Medical University, Yantai, 264003, China. Electronic address:

Acute myeloid leukemia (AML) is the most common acute leukemia affecting adults. The tight junction protein CLDN4 is closely related to the development of various epithelial cell carcinomas. However, whether CLDN4 contributes to AML development remains unclear. Read More

Cancer Immunol Res 2022 Jun 27. Epub 2022 Jun 27.

Dana-Farber Cancer Institute, Boston, MA, United States.

Chimeric-antigen receptor (CAR) T-cell therapy has led to tremendous successes in the treatment of B-cell malignancies. However, a large fraction of treated patients relapse, often with disease expressing reduced levels of the target antigen. Here, we report that exposing CD19+ B-cell acute lymphoblastic leukemia (B-ALL) cells to CD19 CAR T cells reduced CD19 expression within hours. Read More

Proc Natl Acad Sci U S A 2022 Jul 27;119(27):e2123227119. Epub 2022 Jun 27.

Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201.

DNA methyltransferase inhibitors (DNMTis) reexpress hypermethylated genes in cancers and leukemias and also activate endogenous retroviruses (ERVs), leading to interferon (IFN) signaling, in a process known as viral mimicry. In the present study we show that in the subset of acute myeloid leukemias (AMLs) with mutations in , associated with poor prognosis, DNMTis, important drugs for treatment of AML, enable expression of ERVs and IFN and inflammasome signaling in a STING-dependent manner. We previously reported that in solid tumors poly ADP ribose polymerase inhibitors (PARPis) combined with DNMTis to induce an IFN/inflammasome response that is dependent on STING1 and is mechanistically linked to generation of a homologous recombination defect (HRD). Read More

Am J Hematol 2022 Jun 27. Epub 2022 Jun 27.

Cancer Research Center of Lyon, INSERM U1052 and CNRS UMR5286, Lyon, France.

Human endogenous retroviruses (HERVs) represent 8% of the human genome. The expression of HERVs and their immune impact have not been extensively studied in Acute Myeloid Leukemia (AML). In this study, we used a reference of 14,968 HERV functional units to provide a thorough analysis of HERV expression in normal and AML bone marrow cells. Read More

Am J Hematol 2022 Jun 27. Epub 2022 Jun 27.

Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.

Biomacromolecules 2022 Jun 27. Epub 2022 Jun 27.

Cancer Invest 2022 Jun 27:1-6. Epub 2022 Jun 27.

Department of Biotechnology, Motilal Nehru National Institute of Technology Allahabad, Allahabad-211004, India.

Human leukemic T cells show decreased surface CD5 (sCD5) and increased cytoplasmic CD5 (cCD5). When we examined their expressions in the Jurkat T cells, it showed increased sCD5 and decreased cCD5, which is in sharp contrast with the pattern of CD5 expression observed for human leukemic T cells. Furthermore, this opposite pattern was due to the absence of an exonal switch between E1A and E1B. Read More

Leuk Lymphoma 2022 Jun 25:1-11. Epub 2022 Jun 25.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.

This study aims to evaluate the possibility of tyrosine kinase inhibitors (TKIs) discontinuation in chronic myeloid leukemia (CML) patients who obtained sustained deep molecular response (DMR) and to explore the prognostic role of NK cells in treatment-free remission (TFR). Sixty CML patients who discontinued TKI treatment were enrolled, and we also investigated the immune profiles in 27 CML patients after TKI cessation. Of the 60 patients, the estimated TFR rate was 60. Read More

Front Immunol 2022 9;13:889875. Epub 2022 Jun 9.

Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Salamanca, Spain.

Reactive oxygen species (ROS), previously considered toxic by-products of aerobic metabolism, are increasingly recognized as regulators of cellular signaling. Keeping ROS levels low is essential to safeguard the self-renewal capacity of hematopoietic stem cells (HSC). HSC reside in a hypoxic environment and have been shown to be highly dependent on the glycolytic pathway to meet their energy requirements. Read More

Brain Behav Immun Health 2022 Aug 11;23:100480. Epub 2022 Jun 11.

Section of BMT & Cellular Therapies, Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.

Inflammatory physiology has been linked to behavioral and emotional symptoms in a variety of contexts and experimental paradigms. Hematopoietic cell transplantation (HCT) represents an intersection of significant immune dysregulation and psychosocial stress, and this biobehavioral relationship can influence important clinical outcomes. For those undergoing HCT with inflammation-related neuropsychiatric symptoms, using targeted agents such as the IL-6 receptor antagonist tocilizumab may be an effective therapeutic approach. Read More

Front Pediatr 2022 9;10:923297. Epub 2022 Jun 9.

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China.

Acute lymphoblastic leukemia (ALL) presenting with hypercalcemia and osteolytic lesions is rare and unusual in childhood. We report a case of a 13-year-old boy with ALL who presented with intermittent fever, nausea, vomiting, and increasing lower limb pain. Skeletal X-rays and CT scan showed severe osteolytic lesions of the skull and extremities. Read More