A5041497834- Acute Myeloid Leukemia Research
- Retinoids in leukemia and cellular processes
- Acute Lymphoblastic Leukemia research
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Protein Degradation and Inhibitors
- Immune cells in cancer
- Lymphoma Diagnosis and Treatment
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immune Cell Function and Interaction
- Antioxidant Activity and Oxidative Stress
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Neutropenia and Cancer Infections
- Hematopoietic Stem Cell Transplantation
- Childhood Cancer Survivors' Quality of Life
- Telomeres, Telomerase, and Senescence
- Viral-associated cancers and disorders
- Multiple Myeloma Research and Treatments
- CAR-T cell therapy research
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Science and Education Research
- T-cell and Retrovirus Studies
- Cancer, Hypoxia, and Metabolism
Universidade de São Paulo
2016-2025
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
2016-2025
Instituto do Câncer do Estado de São Paulo
2018-2025
D’Or Institute for Research and Education
2021-2024
Fundação Faculdade de Medicina
2004-2024
Fundação de Amparo à Pesquisa do Estado de São Paulo
2020-2024
Fundação Pró-Sangue Hemocentro de São Paulo
2006-2024
Hospital Universitário da Universidade de São Paulo
2020-2023
Clinics Hospital of Ribeirão Preto
2009-2022
Fundação Hemopa
2012-2022
Mutations in DKC1 cause dyskeratosis congenita (DC), a disease characterized by premature aging and increased tumor susceptibility. The protein binds to the box H + ACA small nucleolar RNAs RNA component of telomerase. Here we show that hypomorphic Dkc1 mutant (Dkc1m) mice recapitulate first second generations (G1 G2) clinical features DC. Dkc1m cells from G1 G2 were impaired ribosomal pseudouridylation before onset disease. Reductions telomere length became evident only later generations....
The DKC1 gene encodes a pseudouridine synthase that modifies ribosomal RNA (rRNA). is mutated in people with X-linked dyskeratosis congenita (X-DC), disease characterized by bone marrow failure, skin abnormalities, and increased susceptibility to cancer. How alterations ribosome modification might lead cancer other features of the remains unknown. Using an unbiased proteomics strategy, we discovered specific defect IRES (internal entry site)-dependent translation Dkc1(m) mice cells from X-DC...
Abstract Acute myeloid leukemia remains difficult to treat due strong genetic heterogeneity between and within individual patients. Here, we show that Pyruvate dehydrogenase kinase 1 (PDK1) acts as a targetable determinant of different metabolic states in acute (AML). PDK1 low AMLs are OXPHOS-driven, enriched for leukemic granulocyte-monocyte progenitor (L-GMP) signatures, associated with FLT3 -ITD NPM1 cyt mutations. high however OXPHOS , wild type stemness signatures. Metabolic can even...
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...
Acute promyelocytic leukemia (APL) is associated with chromosomal translocations always involving the RARalpha gene, which variably fuses to one of several distinct loci, including PML or PLZF (X genes) in t(15;17) t(11;17), respectively. APL patients harboring responds well retinoic acid (RA) treatment and chemotherapy, whereas t(11;17) poorly both treatments, thus defining a syndrome. Here, we show that RA, As(2)O(3), RA + As(2)O(3) prolonged survival either leukemic PML-RARalpha...
The promyelocytic leukemia (PML) gene encodes a putative tumor suppressor involved in the control of apoptosis, which is fused to retinoic acid receptor α (RARα) vast majority acute (APL) patients as consequence chromosomal translocations. PMLRARα oncoprotein thought antagonize function PML through its ability heterodimerize with and delocalize from nuclear body. In APL, this may be facilitated by reduction heterozygosity normal allele. To determine whether acts vivo what consequences...
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 Background: The most primitive leukemic precursor in acute myeloid leukemia (AML) is thought to be the stem cell (LSC), which retains properties of self‐renewal and high proliferative capacity quiescence hematopoietic cell. LSC seems immunophenotypically distinct more resistant chemotherapy than committed blasts. Considering that multidrug resistance (MDR) constitutive expression may a barrier therapy AML, we have investigated whether various MDR transporters were differentially...
In the present study, we analyzed AURKA and AURKB gene expression in 70 acute myeloid leukemia (AML) patients. There was no difference between leukemic samples bone marrow mononuclear cells (BMMCs, n = 8) or CD34(+) progenitors (n 10) from healthy donors. High white blood (WBC) counts were observed AURKA(+) AURKB(+) groups, but significant differences regarding age, gender, platelet frequency of FLT3-ITD mutations. AURKA, not AURKB, independently associated with high WBC (OR: 3.15, 95%CI...