A5014445951- Acute Myeloid Leukemia Research
- Retinoids in leukemia and cellular processes
- Protein Degradation and Inhibitors
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Chronic Myeloid Leukemia Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Hemoglobinopathies and Related Disorders
- Histone Deacetylase Inhibitors Research
- Iron Metabolism and Disorders
- Erythrocyte Function and Pathophysiology
- Autophagy in Disease and Therapy
- Bone and Joint Diseases
- Cancer, Hypoxia, and Metabolism
- Kruppel-like factors research
- Glioma Diagnosis and Treatment
- Cancer-related gene regulation
- Cell death mechanisms and regulation
- Ubiquitin and proteasome pathways
- Immune Cell Function and Interaction
- Microfinance and Financial Inclusion
- Cancer Research and Treatments
- PARP inhibition in cancer therapy
- Biochemical and Molecular Research
- Healthcare during COVID-19 Pandemic
University Medical Center Groningen
2020-2024
Universidade de São Paulo
2017-2024
University of Groningen
2020-2024
King's College London
2024
Blood Cancer UK
2024
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
2024
Zero to Three
2023
Fundação Hemopa
2019-2023
Fundação de Amparo à Pesquisa do Estado de São Paulo
2022
Clinics Hospital of Ribeirão Preto
2020-2021
It is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor clones. Combined single-cell RNA sequencing, flow cytometry, immunohistochemistry studies the innate immune compartment in bone marrow patients with acute myeloid leukemia (AML) reveal shift toward tumor-supportive M2-polarized macrophage landscape an altered transcriptional program, enhanced fatty acid oxidation NAD+ generation. Functionally, these AML-associated macrophages display decreased...
Abstract Metabolic programs can differ substantially across genetically distinct subtypes of acute myeloid leukemia (AML). These are not static entities but change swiftly as a consequence extracellular changes or in response to pathway-inhibiting drugs. Here, we uncover that AML patients with FLT3 internal tandem duplications ( -ITD + ) characterized by high expression succinate-CoA ligases and activity mitochondrial electron transport chain (ETC) complex II, thereby driving respiration...
Abstract The treatment of acute leukemia is challenging because the genetic heterogeneity between and within patients. Leukemic stem cells (LSCs) are relatively drug-resistant frequently relapse. Their plasticity capacity to adapt extracellular stress, in which mitochondrial metabolism autophagy play important roles, further complicates treatment. Genetic models phosphatidylinositol-5-phosphate 4-kinase type 2 protein (PIP4K2s) inhibition have demonstrated relevance these enzymes homeostasis...
Despite advancements in utilizing genetic markers to enhance acute myeloid leukaemia (AML) outcome prediction, significant disease heterogeneity persists, hindering clinical management. To refine survival predictions, we assessed the transcriptome of non-acute promyelocytic chemotherapy-treated AML patients from five cohorts (n = 975). This led identification a 4-gene prognostic index (4-PI) comprising CYP2E1, DHCR7, IL2RA and SQLE. The 4-PI effectively stratified into risk categories, with...
The SLIT-ROBO axis plays an important role in normal stem-cell biology, with possible repercussions on cancer stem cell emergence. Although the Promyelocytic Leukemia (PML) protein can regulate SLIT2 expression central nervous system, little is known about acute promyelocytic leukemia. Hence, we aimed to investigate levels of leukemia (APL) and assess its biological activity vitro vivo. Our analysis indicated that blasts SLIT2high transcript were associated cycle arrest, while SLIT2low APL...
In approximately 15% of patients with acute myeloid leukemia (AML), total and phosphorylated EGFR proteins have been reported to be increased compared healthy CD34+ samples. However, it is unclear if this subset would benefit from signaling pharmacological inhibition. Pre-clinical studies on AML cells provided evidence the pro-differentiation benefits inhibitors when combined ATRA or ATO in vitro. Despite success treatment promyelocytic (APL), therapy-associated resistance observed 5-10%...
Abstract Although the mixed lineage leukemia 5 ( MLL5 ) gene has prognostic implications in acute promyelocyte (APL), underlying mechanism remains to be elucidated. Here, we demonstrate critical role exerted by APL regarding cell proliferation and resistance drug-induced apoptosis, through mtROS regulation. Additionally, overexpression increased responsiveness of leukemic cells all-trans retinoic acid (ATRA)-induced differentiation, via regulation epigenetic modifiers SETD7 LSD1 . In silico...
Sickle cell anemia (SCA) is a Mendelian disorder with heterogeneous clinical course. The reasons for this phenotypic diversity are not entirely established, but it known that high fetal hemoglobin levels lead to milder course of the disease. Additionally, genetic variants in intergenic region HBS1L-MYB promote into adulthood. In present study, we investigated HMIP1 C-839A (rs9376092) polymorphism, located at block 1, SCA patients. We analyzed 299 patients followed two reference centers...
Abstract While it is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor clones, the microenvironment (TME) in acute myeloid leukemias (AML) remains poorly understood. Here, we uncover functional prognostic relevance an M2-polarized macrophage compartment. Intra bone marrow co-injection M2d-macrophages together with leukemic blasts fail to engraft on their own now induce fatal leukemia mice. Even short-term two-day vitro exposure M2d macrophages can...
Summary Although a growing body of evidence demonstrates that altered mtDNA content (mtDNAc) has clinical implications in several types solid tumours, its prognostic relevance acute promyelocytic leukaemia (APL) patients remains largely unknown. Here, we show with higher‐than‐normal mtDNAc had better outcomes regardless tumour burden. These results were more evident low‐risk relapse. The multivariate Cox proportional hazard model demonstrated high was independently associated decreased...
Several laboratory and clinical variables have been reported to be associated with the outcome of intensive chemotherapy for acute myeloid leukemia (AML), but only a few tested in context hematopoietic stem cell transplant (HSCT). This study aimed identify genes whose expression AML at diagnosis were survival after HSCT. For this purpose, three publicly available adult cohorts (TCGA, BeatAML, HOVON), patients treated then subjected allogeneic or autologous HSCT, included study. After whole...