Treatment options are limited for patients with advanced forms of myeloproliferative neoplasms (MPN) including blast-phase disease (MPN-BP). Decitabine has frequently been deployed but its efficacy and safety profile are not well described in this population. We retrospectively reviewed 42 patients treated with decitabine either alone or in combination with ruxolitinib at our institution: 16 with MPN-BP, 14 with MPN accelerated-phase (MPN-AP), and 12 with myelofibrosis with high-risk features (MF-HR). The median overall survival (OS) for the MPN-BP patients was 2.6 months, and for those who received ≥2 cycles of decitabine therapy, it was 6.7 months (3.8-29.8). MPN-BP patients with a poor performance status and who required hospitalization at the time of the initiation of decitabine had a dismal prognosis. After a median follow-up of 12.4 months for MPN-AP patients, and 38.7 months for MF-HR patients, the median OS was not reached for either cohort, with 1 and 2 patients alive at 60 months, respectively. The probability of spleen length reduction and transfusion independence within 12 months of initiating decitabine was 28.6 and 23.5%, respectively. The combination of decitabine and ruxolitinib appeared to improve overall survival versus single-agent decitabine (21 and 12.9 months, respectively). Decitabine, alone or in combination with ruxolitinib, appears to have clinical benefit for patients with advanced phases of MPN when initiated early in the disease course prior to the development of MPN-BP.
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http://dx.doi.org/10.1159/000506146 | DOI Listing |
Genes (Basel)
December 2024
Department of Bioinformatics, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
Epigenetic dysregulation is a common feature of cancer. Promoter demethylation of tumor-promoting genes and global DNA hypomethylation may trigger tumor progression. Epigenetic changes are unstable; thus, research has focused on detecting remedies that target epigenetic regulators.
View Article and Find Full Text PDFMol Oncol
January 2025
Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Germany.
Hypermethylation of tumor suppressor genes is a hallmark of leukemia. The hypomethylating agent decitabine covalently binds, and degrades DNA (cytosine-5)-methyltransferase 1 (DNMT1). Structural similarities within DNA-binding domains of DNMT1, and the leukemic driver histone-lysine N-methyltransferase 2A (KMT2A) suggest that decitabine might also affect the latter.
View Article and Find Full Text PDFFront Oncol
December 2024
Department of Hematology, The 923rd Hospital of the Joint Logistics Support Force of the People's Liberation Army, Nanning, China.
The management of patients with myelodysplastic syndrome (MDS) refractory to hypomethylating agents (HMAs) remains a challenge with few reliably effective treatments. Preclinical studies have shown that the inhibition of the nuclear export protein XPO1 causes nuclear accumulation of p53 and disruption of NF-κB signaling; both of which are relevant targets for MDS. Selinexor is an XPO1 inhibitor with demonstrated efficacy in MDS patients.
View Article and Find Full Text PDFJ Adv Res
December 2024
State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. Electronic address:
Introduction: The periodontal ligament (PDL), a dynamic connective tissue that anchors teeth to the alveolar bone, enables tooth retention and facilitates continuous turnover. The integrity of the periodontium is maintained by periodontal ligament stem cells (PDLSCs), whose dysfunction and senescence with age can disrupt tissue homeostasis, hinder injury repair, and lead to tooth loss, ultimately impacting overall health. Transforming growth factor-β1 (TGF-β1) is known for its regenerative properties and as a functional paracrine factor in stem cell therapy, but its precise role in modulating PDLSC activity remains controversial and poorly understood.
View Article and Find Full Text PDFBMC Med
December 2024
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended for patients with KMT2A-rearranged (KMT2A-r) leukemia whereas relapse remains high. We aimed to determine whether intensified conditioning containing decitabine (Dec) could reduce relapse compared with standard myeloablative conditioning in adult patients with KMT2A-r leukemia.
Methods: We performed a multicenter retrospective study at seven institutions in China.
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