A5090333475- Acute Myeloid Leukemia Research
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- RNA modifications and cancer
- Circular RNAs in diseases
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Mycobacterium research and diagnosis
- Hemoglobinopathies and Related Disorders
- Acute Lymphoblastic Leukemia research
- Extracellular vesicles in disease
- Molecular Biology Techniques and Applications
- Chronic Myeloid Leukemia Treatments
- Drug Transport and Resistance Mechanisms
- HIV/AIDS drug development and treatment
- Cancer Genomics and Diagnostics
- Advanced biosensing and bioanalysis techniques
- Cytokine Signaling Pathways and Interactions
- Telomeres, Telomerase, and Senescence
- Chromosomal and Genetic Variations
- Eosinophilic Disorders and Syndromes
- RNA Interference and Gene Delivery
- Vascular Tumors and Angiosarcomas
Institute of Haematology and Blood Transfusion
2019-2025
Abstract Background Myelodysplastic neoplasms (MDS) are heterogeneous hematopoietic disorders characterized by ineffective hematopoiesis and genome instability. Mobilization of transposable elements (TEs) is an important source instability leading to oncogenesis, whereas small PIWI-interacting RNAs (piRNAs) act as cellular suppressors TEs. However, the roles TEs piRNAs in MDS remain unclear. Methods In this study, we examined TE piRNA expression through parallel RNA sequencing CD34+ stem...
Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders with large heterogeneity at the clinical and molecular levels. As diagnostic procedures shift from bone marrow biopsies towards less invasive techniques, circulating small noncoding RNAs (sncRNAs) have become of particular interest as potential novel noninvasive biomarkers disease. We aimed to characterize expression profiles sncRNAs MDS patients search for specific applicable biomarkers. performed RNA-seq in paired...
Abstract Patients with lower-risk myelodysplastic syndromes (LR-MDS) have a generally favorable prognosis; however, small proportion of cases progress rapidly. This study aimed to define molecular biomarkers predictive LR-MDS progression and uncover cellular pathways contributing malignant transformation. The mutational landscape was analyzed in 214 patients, at least one mutation detected 137 patients (64%). Mutated RUNX1 identified as the main predictor rapid by statistics machine...
Background: myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder with an incompletely known pathogenesis. Long noncoding RNAs (lncRNAs) play multiple roles in hematopoiesis and represent new class of biomarkers therapeutic targets, but information on their MDS limited. Aims: here, we aimed to characterize lncRNAs deregulated that may function disease In particular, focused the identification could serve as novel potential adverse outcomes MDS. Methods: performed microarray...
To date, no chemoresistance predictors are included in acute myeloid leukaemia (AML) prognostic scoring systems to distinguish responding and refractory AML patients prior chemotherapy. ABC transporters have been described as altering chemosensitivity; however, a relevant study investigating their role at various molecular levels was lacking.
Abstract Background Multiple studies have reported the prognostic impact of DNA methylation changes in acute myeloid leukemia (AML). However, these epigenetic markers not been thoroughly validated and therefore are still considered clinical practice. Hence, we aimed to independently verify results selected describing relationship between specific genes their potential predicting overall survival (OS) event-free (EFS). Results Fourteen (published 2011–2019) comprising 27 were subjected...
Mutations in the splicing factor 3b subunit 1 ( SF3B1 ) gene are frequent myelodysplastic neoplasms (MDS). Because process is involved production of circular RNAs (circRNAs), we investigated impact mutations on circRNA processing. Using RNA sequencing, measured expression CD34+ bone marrow MDS cells. We defined circRNAs deregulated a heterogeneous group patients and described increased formation higher‐risk MDS. showed that presence did not affect global circRNAs; however, deregulation...
Abstract Patients with myelodysplastic neoplasms (MDS) are classified according to the risk of acute myeloid leukemia transformation. Some lower‐risk MDS patients (LR‐MDS) progress rapidly despite expected good prognosis. Using diagnostic samples, we aimed uncover mechanisms this accelerated progression at transcriptome level. RNAseq was performed on CD34+ ribodepleted RNA samples from 53 LR‐MDS without (stMDS) and 8 who progressed within 20 months (prMDS); 845 genes were differentially...
Prediction of response to azacitidine (AZA) treatment is an important challenge in hematooncology. In addition protein coding genes (PCGs), AZA efficiency influenced by various noncoding RNAs (ncRNAs), including long ncRNAs (lncRNAs), circular (circRNAs), and transposable elements (TEs).RNA sequencing was performed patients with myelodysplastic syndromes or acute myeloid leukemia before assess contribution mechanisms propose novel disease prediction biomarkers.Our analyses showed that...
Somatic mutations are a common molecular mechanism through which chronic myeloid leukemia (CML) cells acquire resistance to tyrosine kinase inhibitors (TKIs) therapy. While most of the in domain BCR-ABL1 can be successfully managed, recurrent somatic other genes may therapeutically challenging. Despite major clinical relevance mutation-associated CML, mechanisms underlying mutation acquisition TKI-treated leukemic not well understood. This work demonstrated de novo on isolated single-cell...
Deferasirox (DFX) is an oral iron chelator used to reduce overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms which DFX improves outcome MDS, we analyzed global gene expression untreated MDS patients and those who were given treatment. The profiles of bone marrow CD34+ cells assessed whole-genome microarrays. Initially, differentially expressed genes (DEGs) determined between with normal ferritin levels...
Abstract Background Changes in DNA methylation are common events the pathogenesis of acute myeloid leukemia (AML) and have been repeatedly reported as associated with prognosis. However, studies integrating these numerous potentially prognostically relevant changes lacking. Therefore, we aimed for an overall evaluation epigenetic aberrations to provide a comprehensive NGS-based approach assessment AML prognostication. Results We designed sequencing panel targeting 239 regions (approx. 573 kb...
Somatic JAK2 mutations are the main molecular cause of vast majority polycythemia vera (PV) cases. According to a recent structural model, prevalent acquired V617F mutation improves stability dimer, thereby enhancing constitutive kinase activity. Germline usually do not largely alter signaling, although they may modulate impact V617F. We found an unusual germline L604F in homozygous form young PV patient, along with low allele burden mutation, and her apparently healthy sister. Their father...
To better understand the molecular basis of resistance to azacitidine (AZA) therapy in myelodysplastic syndromes (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), we performed RNA sequencing on pre-treatment CD34+ hematopoietic stem/progenitor cells (HSPCs) isolated from 25 MDS/AML-MRC patients discovery cohort (10 AZA responders (RD), six stable disease, nine progressive disease (PD) during therapy) eight controls. Eleven samples were also available for...
Background: Approximately 40 % of acute myeloid leukemia (AML) patients does not achieve a complete hematologic remission (CR) after the first cycle 3 + 7 induction therapy and thus face an adverse prognosis. Mechanisms chemoresistance are still poorly understood, but drug export from cytosol plays crucial role. ABC transporters (ABCA2, ABCA5, ABCB1, ABCB6, ABCC1, ABCC3, ABCG2) were selected literature for expression, methylation, genotype efflux activity analysis. Aims: The aim this study...
Background: Prediction of response to azacitidine (AZA) treatment is an important challenge in the management higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). To date, no clinical, cytogenetic, or molecular markers AZA outcome have been validated support clinical decisions. Moreover, little known about how efficiency can be affected by various noncoding RNAs (ncRNAs), such as long ncRNAs (lncRNAs) circular (circRNAs). KDM genes encode demethylases histone lysine...