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Predictors of severity and new treatments for bone marrow neoplasias

Grant number: 17/21801-2
Support type:Research Projects - Thematic Grants
Duration: April 01, 2019 - March 31, 2024
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Sara Teresinha Olalla Saad
Grantee:Sara Teresinha Olalla Saad
Home Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Principal researchers:Gisele Wally Braga Colleoni ; Mary Ann Foglio
Assoc. researchers:Anamika Dhyani ; Bruno Deltreggia Benites ; Cristiane Okuda Torello ; Fernanda Marconi Roversi ; Fernando Vieira Pericole de Souza ; João Ernesto de Carvalho ; Mariana Lazarini ; Paula de Melo Campos ; Simone Cristina Olenscki Gilli
Associated scholarship(s):21/05132-9 - Severity predictors and new treatments for bone marrow neoplasms, BP.IC
21/03320-2 - Avaliação de indivíduos com citopenia clonal de significado incerto, BP.IC
20/09208-7 - Predictors of severity and new treatments for Bone Marrow Neoplasias, BP.PD
+ associated scholarships 20/10771-8 - Predictors of severity and new treatments for bone marrow neoplasias/medullary fibrosis in chronic myeloproliferative neoplasms: inflammation and niche, BP.IC
20/04133-9 - Predictors of severity and new treatments for bone marrow neoplasias: mechanisms by which quercetin, epigallocatechin 3-gallate, gallic acid, turmeric, artemisimine and derivatives modulate epigenetic changes and energy metabolism in myelodysplasia, BP.PD
20/05553-1 - Predictors of severity and new treatments for bone marrow neoplasias, BP.IC
19/25247-5 - Study of inhibitory and antitumor activity of natural substance-associated MAPK and WNT inhibitors in in vitro models, BP.TT
19/18560-9 - ARHGAP21 in angiogenesis, BP.PD
19/21849-0 - Evaluation of the Pterodon pubescens Benth, Arrabidaea chica Verlot and Bixa Orellana fruit extracts association in healing and antiproliferative activities, BP.TT
19/20080-5 - Development of bioinformatics tools for analysis and visualization of proteomics and genomics data, BP.TT
19/18529-4 - Basic training in cell biology techniques, BP.TT
19/18410-7 - Evaluation of the association of extracts of Pterodon pubescens Benth.fruits, Arrabidaea chica Verlot and Bixa orellana in healing, antinociceptive and anti-inflammatory activities, BP.IC
19/12273-8 - Evaluation of the association of fruit extracts of Pterodon pubescens, Arrabidaea chica Verlot and Bixa orellana on healing and antiproliferative activities, BP.IC
19/13920-7 - Standardization and optimization of commercial kit for diagnosis of rearrangements b2a2 and b3a2 of the gene BCR/ABL: discontinuation of tyrosine kinase inhibitor in good prognosis patients with chronic myeloid leukemia, BP.IC
19/12689-0 - Medullary fibrosis in chronic myeloproliferative neoplasms: inflammation and niche, BP.TT
15/18574-9 - Screening of mutations related to hereditary anemias using NGS-Targeted sequencing panel, BP.PD
15/21164-7 - Analysis of the mechanisms by which polyphenols epigallocatechin 3 gallate and Quercetin modulate epigenetic alterations present in leukemias and myelodysplastic syndromes, BP.PD - associated scholarships


Bone marrow neoplasias are aggressive disorders with low healing potential. As the incidence of cancer increases with age, a growing number of older individuals are receiving therapy for cancer and frequently in intensive modalities. As these older patients tend to present comorbidities, treatment decisions can often become difficult due to their fragile physical state which may affect therapy tolerability and efficiency against cancer. The toxicity related to the treatment and long periods of hospitalization, often required, have a profound impact upon the quality of life of these patients. However, most elderly individuals and family members consider quality of life a priority. Additionally, extended treatments deplete the financial resources of both public and private health systems, and the extra costs also deplete the family´s financial reserves. In light of the foregoing, the present study will address novel therapeutic forms and severity predictors which could aid in therapy decision taking of the following bone marrow neoplasias: acute myeloid leukemia (AML) myelodysplastic syndromes (MDS), multiple myeloma (MM) and primary myelofibrosis (PMF). These disorders have a common characteristic which is the fatal course of the disease and the lack of efficient therapeutic options, where bone marrow transplantation represents the only curative therapy or therapy capable of extending survival, despite not being indicated for older patients or those with many comorbidities. Therefore, a number of issues could be clarified by this study: * What would be the effect of natural products, which have been demonstrated to be inductor agents of cell death or cell cycle arrest, upon the treatment of these disorders? These compounds have a known action of inducing or inhibiting reactive oxygen species (ROS) and/or nitric oxide and can have a direct effect upon the induction of neoplasia cell death or modulate cell immunity.*Would elderly patients have a better survival and quality of life were they to be treated with less aggressive therapies with less side effects? *Could mesenchymal cells or metformin reduce bone marrow fibrosis? *Would dendritic cell vaccines for AML and MM patients in remission, be an alternative for reducing disease recurrence? *Could severity markers for the aforementioned disorders, identified in our previous studies, be the targets of specific therapies? *Would the production of universal in vitro platelets to improve the support therapy of these patients be possible? This choice of investigation is a result of our dissatisfaction in observing that most patients with bone marrow neoplastic disorders are not candidates for last-generation treatments. Furthermore, the lack of hospital beds and the impossibility of using high cost antibiotics and immunobiologicals in the unified public health system (SUS) point to the need of performing high level research to seek alternatives to enable us, in the short-term, to face the reality of many patients who have no access to clinical studies with new high cost drugs, not only in Brazil, but throughout the World. For this investigation, we will carry out pre-clinical trials, using leukemia, myelodysplastic and xenogeneic tumor animal models, and phase I and II clinical studies. We will further standardize the production method of universal platelets, to enable better support for patients with severe bone marrow failure in consequence of hematologic neoplasia. (AU)

Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MANCUSO, RUBIA ISLER; OLALLA SAAD, SARA TERESINHA; AZAMBUJA, JULIANA HOFSTATTER. Artesunate Switches Monocytes to an Inflammatory Phenotype with the Ability to Kill Leukemic Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 2 JAN 2021. Web of Science Citations: 0.
COTRIM GUERREIRO DA SILVA, ISMAEL DALE; DE CASTRO LEVATTI, ERICA VALADARES; PEDROSO, AMANDA PAULA; LOBO MARCHIONI, DIRCE MARIA; FERREIRA CARIOCA, ANTONIO AUGUSTO; BRAGA COLLEONI, GISELE WALLY. Biochemical phenotyping of multiple myeloma patients at diagnosis reveals a disorder of mitochondrial complexes I and II and a Hartnup-like disturbance as underlying conditions, also influencing different stages of the disease. SCIENTIFIC REPORTS, v. 10, n. 1 DEC 14 2020. Web of Science Citations: 0.
MANCUSO, I, R.; FOGLIO, M. A.; SAAD, S. T. OLALLA. Artemisinin-type drugs for the treatment of hematological malignancies. Cancer Chemotherapy and Pharmacology, v. 87, n. 1 NOV 2020. Web of Science Citations: 1.
DE PAIVA, PAULA P.; NUNES, JULIA H. B.; NONATO, FABIANA R.; RUIZ, ANA L. T. G.; ZAFRED, RAFAEL R. T.; SOUSA, ILZA M. O.; OKUBO, MARCIA Y.; KAWANO, DANIEL F.; MONTEIRO, PAULA A.; FOGLIO, MARY A.; CARVALHO, JOAO E. In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained fromBoehmeria caudataSw. Aerial Parts. Molecules, v. 25, n. 17 SEP 2020. Web of Science Citations: 0.
BENITES, BRUNO DELTREGGIA; ALVAREZ, MARISA CLAUDIA; OLALLA SAAD, SARA TERESINHA. Small Particles, Big Effects: The Interplay Between Exosomes and Dendritic Cells in Antitumor Immunity and Immunotherapy. CELLS, v. 8, n. 12 DEC 2019. Web of Science Citations: 0.
BARBOSA, REBECCA S. S.; DANTONIO, PAOLA M.; GUIMARAES, TAIS; DE OLIVEIRA, MARIANA B.; FOOK ALVES, VERUSKA L.; SANDES, ALEX FREIRE; FERNANDO, RODRIGO CARLINI; COLLEONI, GISELE W. B. Sequential combination of bortezomib and WEE1 inhibitor, MK-1775, induced apoptosis in multiple myeloma cell lines. Biochemical and Biophysical Research Communications, v. 519, n. 3, p. 597-604, NOV 12 2019. Web of Science Citations: 0.

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