Cancers, Vol. 12, Pages 2891: Novel Concepts of Treatment for Patients with Myelofibrosis and Related Neoplasms

Cancers, Vol. 12, Pages 2891: Novel Concepts of Treatment for Patients with Myelofibrosis and Related Neoplasms Cancers doi: 10.3390/cancers12102891 Authors: Prithviraj Bose Lucia Masarova Srdan Verstovsek Janus kinase (JAK) inhibition forms the cornerstone of the treatment of myelofibrosis (MF), and the JAK inhibitor ruxolitinib is often used as a second-line agent in patients with polycythemia vera (PV) who fail hydroxyurea (HU). In addition, ruxolitinib continues to be studied in patients with essential thrombocythemia (ET). The benefits of JAK inhibition in terms of splenomegaly and symptoms in patients with MF are undeniable, and ruxolitinib prolongs the survival of persons with higher risk MF. Despite this, however, “disease-modifying” effects of JAK inhibitors in MF, i.e., bone marrow fibrosis and mutant allele burden reduction, are limited. Similarly, in HU-resistant/intolerant PV, while ruxolitinib provides excellent control of the hematocrit, symptoms and splenomegaly, reduction in the rate of thromboembolic events has not been convincingly demonstrated. Furthermore, JAK inhibitors do not prevent disease evolution to MF or acute myeloid leukemia (AML). Frontline cytoreductive therapy for PV generally comprises HU and interferons, which have their own limitations. Numerous novel agents, representing diverse mechanisms of action, are in development for the treatment of these three classic myeloproliferative neoplasms (MPNs). JAK inhibit...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research

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Corcos Eric Lippert Since the discovery of spliceosome mutations in myeloid malignancies, abnormal pre-mRNA splicing, which has been well studied in various cancers, has attracted novel interest in hematology. However, despite the common occurrence of spliceosome mutations in myelo-proliferative neoplasms (MPN), not much is known regarding the characterization and mechanisms of splicing anomalies in MPN. In this article, we review the current scientific literature regarding “splicing and myeloproliferative neoplasms”. We first analyse the clinical series reporting spliceosome mutations in MPN and ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
AbstractPurpose of ReviewKnowledge of both somatic mutations and copy number aberrations are important for the understanding of cancer pathogenesis and management of myeloid neoplasms. The currently available standard of care technologies for copy number assessment such as conventional karyotype and FISH are either limited by low resolution or restriction to targeted assessment.Recent FindingsChromosomal microarray (CMA) is effective in characterization of chromosomal and gene aberrations of diagnostic, prognostic, and therapeutic significance at a higher resolution than conventional karyotyping. These results are compleme...
Source: Current Hematologic Malignancy Reports - Category: Hematology Source Type: research
CONCLUSION: NGAL was related to neutrophil count and VEGF. NGAL and VEGF showed similar intergroup patterns, reflecting that NGAL was associated with VEGF. PMID: 32304694 [PubMed - as supplied by publisher]
Source: Clinical Biochemistry - Category: Biochemistry Authors: Tags: Clin Biochem Source Type: research
TheASXL1 mutation frequency is high in AML ‐MRC patients being its presence associated with specific characteristics, including morphological signs of dysplasia. This association raises the possible role ofASXL1 as a surrogate marker in AML ‐MRC, which could facilitate the diagnosis of patients within this group when the karyotype is normal, and especially when the assessment of multilineage dysplasia morphologically is difficult. This mutation could be used as a worst outcome marker in de novo AML‐MRC with intermediate‐risk kar yotype. AbstractAcute myeloid leukemia with myelodysplasia ‐related changes (AML...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Cells become senescent in response to a variety of circumstances. The vast majority are cases of replicative senescence, somatic cells reaching the Hayflick limit. Cell damage and toxic environments also produce senescence, and senescent cells are also created as a part of the wound healing process. A senescent cell ceases replication and begins to secrete inflammatory and pro-growth signals, altering the nearby extracellular matrix and behavior of surrounding cells - even encouraging them to become senescent as well. Near all senescent cells last a short time only, as they self-destruct or are removed by the immune...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
T cell cancer neoantigens are created from peptides derived from cancer-specific aberrant proteins, such as mutated and fusion proteins, presented in complex with human leukocyte antigens on the cancer cell surface. Because expression of the aberrant target protein is exclusive to malignant cells, immunotherapy directed against neoantigens should avoid “on-target, off-tumor” toxicity. The efficacy of neoantigen vaccines in melanoma and glioblastoma and of adoptive transfer of neoantigen-specific T cells in epithelial tumors indicates that neoantigens are valid therapeutic targets. Improvements in sequencing tec...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
We analyzed the clinical characteristics, laboratory characteristics, cytogenetics, thromboembolism status, disease progression, and overall survival of 1537 Chinese MPN patients with the JAK2V617F mutation. The multivariate analysis indicated that age ≥60 years old, HCT ≥48%, at least one cardiovascular risk factor, history of thrombosis, and JAK2V617F allele burden (V617F%) ≥50% are risk factors for thrombosis of JAK2V617F‐mutated MPN. Our study suggested that for elderly patients with JAK2V617F‐mutated MPN and a history of thrombosis, reducingV617F%, controlling HCT, and mitigating cardiovascular risk ...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
This study, we evaluated the circulatory levels of microRNA-29a-3p (miR-29a-3p) and miR-92a-3p beside exploring the expression pattern of their target gene myeloid cell leukemia sequence1 (MCL1) to investigate the role of these molecules in AML pathophysiology and to assess their ability to diagnose AML patients. METHODS: 40 adult AML patients along with 20 healthy subjects were enrolled in this study. Plasma were separated from venous blood samples, collected on EDTA, of all individuals were used to assess circulating miRNAs' levels. In the meantime, total RNA was extracted from isolated leukocytes and was used to qua...
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
This study is registered with Clinicaltrials.gov, number NCT02560025, and has completed enrolment.FindingsBetween Dec 31, 2015, and Aug 1, 2017, we enrolled a total of 39 eligible patients. 19 (49%) of 39 patients had secondary acute myeloid leukaemia and three (8%) had therapy-related acute myeloid leukaemia. At mid-induction, 33 (85%) of 39 patients showed marrow aplasia, six (15%) received re-induction. The median follow-up was 13·7 months (IQR 12·7–14·4). Composite remission was 64% (two-stage 95% CI 48–79), with 20 (51%) of 39 patients achieving complete remission and five (13%) achiev...
Source: The Lancet Haematology - Category: Hematology Source Type: research
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