Biology of neoplastic diseases of bone marrow

• Grant number: 11/51959-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: December 01, 2012
• End date: September 30, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Sara Teresinha Olalla Saad
• Grantee: Sara Teresinha Olalla Saad
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Pesquisadores principais: Carlos Lenz Cesar ; Fabíola Traina ; Patricia Maria Bergamo Favaro
• Associated research grant(s): 14/50153-0 - Investigation of novel cell functions of ARHGAP21 and ANKHD1 proteins, AP.R
• Associated scholarship(s): 16/14276-6 - Role of ARHGAP21 in the medullary stroma, maintenance of hematopoiesis in vitro and in the CXCL12/CXCR4 signaling pathway in vivo, BP.PD; 15/05780-0 - Evaluation of the influence of polymorphism in the gene encoding multidrug resistance protein 2 (Mrp2) in iron chelator toxicity profile Deferasirox., BP.IC; 14/23570-0 - Investigation of the antioxidant activity of EGCG upon leukemia cells, BP.PD; + associated scholarships 14/16026-1 - Investigation of biological and pharmacological effects of Chlorella vulgaris extract in xenografic tumors derived from leukemic cell lines, BP.IC; 14/08939-7 - Antioxidant potential of green tea in the quiescence/mobilization of hematopoietic cells mediated by oxidative stress and standardization of an experimental model for leukemia, BP.PD; 13/20657-4 - Investigation of the etv6 gene mutations in patients with myelodysplastic Syndromes, BP.IC; 13/21539-5 - Investigation of the effects of Rhodiola rosea and green tea (Camellia sinensis) extracts in animals transplanted with the U037 leukemia strain, BP.IC; 12/10929-4 - ROLE OF ANKHD1 IN MULTIPLE MYELOMA PROGRESSION AND THERAPY, BP.PD; 11/22376-7 - Investigation deregulated pathways in myelodysplasia and acute leukemia from previous results obtained using microarray, BP.PD - associated scholarships

Abstract

The present project aims at investigating the factors involved in the self-renewal and maintenance of bone marrow neoplastic cells, as occurs in myelodysplasia, acute leukemias, and multiple myeloma. The common aspect between them all is that they all occur in high frequency in the population, and despite the considerable therapeutic advances achieved during the last decade, still have a poor prognosis. Therefore, complete remission of acute leukemia in adults is below 50%, and those who are not cured during the first year, rapidly succumb to the disease. In multiple myeloma and myelodysplasias, complete remission occurs in the minority of the cases and the only potentially curative option is allogeneic bone marrow transplantation Another important aspect of these disorders is that they are all related to the reciprocal interaction between the neoplastic cell and the microenvironment of the bone marrow, which regulate differentiation, proliferation, and the survival of neoplastic cells. In this project, the focus will be maintained upon the molecular mechanisms of these interactions, the study of epigenetic changes, and functional characterization of novel proteins involved in the pathogenesis of these disorders. For this purpose, we will investigate the aspects of the bone marrow niche which can facilitate the self-renewal of neoplastic cells, as well as the immunomodulatory effect of the bone marrow stroma upon the development of neoplasias and the autophagy process. Furthermore, we will continue the characterization of novel proteins previously described by our group and in full development such as ARHGAP21 and ANKHD1, and any other candidates which by chance may be discovered throughout the project, as a result from the latest generation of sequencing of specific cases We will also continue with the investigation of coding and non-coding transcripts, deregulated in the stroma and CD34+ cells of myelodysplasia patients, as published by our group. Novel drugs which are still being developed and patented by groups from UNICAMP or other groups, will also be an object of study. (AU)

Scientific publications

(32)

(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)

CALGAROTTO, ANDRANA K.; LONGHINI, ANA L.; PERICOLE DE SOUZA, FERNANDO V.; DUARTE, ADRIANA S. SANTOS; FERRO, KARLA P.; SANTOS, IRENE; MASO, VICTOR; OLALLA SAAD, SARA T.; TORELLO, CRISTIANE OKUDA. mmunomodulatory Effect of Green Tea Treatment in Combination with Low-dose Chemotherapy in Elderly Acute Myeloid Leukemia Patients with Myelodysplasia-related Change. INTEGRATIVE CANCER THERAPIES, v. 20, MAR 2021. (12/06675-7, 11/51959-0)

XAVIER-FERRUCIO, JULIANA; RICON, LAUREMILIA; VIEIRA, KARLA; LONGHINI, ANA LEDA; LAZARINI, MARIANA; BIGARELLA, CAROLINA LOUZAO; FRANCHI, JR., GILBERTO; KRAUSE, DIANE S.; SAAD, SARA T. O.. Hematopoietic defects in response to reduced Arhgap21. STEM CELL RESEARCH, v. 26, p. 17-27, JAN 2018. (09/08908-6, 11/51959-0)

PALODETTO, BRUNA; SANTOS DUARTE, ADRIANA DA SILVA; LOPES, MATHEUS RODRIGUES; CORROCHER, FLAVIA ADOLFO; ROVERSI, FERNANDA MARCONI; NIEMANNI, FERNANDA SOARES; VIEIRA FERRO, KARLA PRISCILA; FIGUEIREDO LONGHINI, ANA LEDA; CAMPOS, PAULA MELO; FAVARO, PATRICIA; et al. SEMA3A partially reverses VEGF effects through binding to neuropilin-1. STEM CELL RESEARCH, v. 22, p. 70-78, JUL 2017. (11/51959-0)

BERNUSSO, VANESSA A.; MACHADO-NETO, JOAO A.; PERICOLE, FERNANDO V.; VIEIRA, KARLA P.; DUARTE, ADRIANA S. S.; TRAINA, FABIOLA; HANSEN, MARC D.; SAAD, SARA T. OLALLA; BARCELLOS, KARIN S. A.. Imatinib restores VASP activity and its interaction with Zyxin in BCR-ABL leukemic cells. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1853, n. 2, p. 388-395, FEB 2015. (08/57895-1, 11/51959-0, 11/14498-5)

ALMEIDA, DIOGO B.; DE THOMAZ, ANDRE A.; CARVALHO, HERNANDES F.; CESAR, CARLOS L.. One- and two-photon photoluminescence excitation spectra of CdTe quantum dots in a cryogenic confocal microscopy platform. Optics Express, v. 23, n. 15, p. 19715-19727, JUL 27 2015. (05/51689-2, 11/51959-0)

CORROCHER, FLAVIA ADOLFO; DE PAIVA, LUCIANA BUENO; SANTOS DUARTE, ADRIANA SILVA; FERRO, KARLA PRISCILA; SILVEIRA, LEONARDO DOS REIS; DE LIMA, TANES IAMAMURA; OLALLA SAAD, SARA TERESINHA; LAZARINI, MARIANA. Reduced expression of NR4A1 activates glycolytic pathway in acute promyelocytic leukemia cells. Leukemia & Lymphoma, v. 59, n. 6, p. 1501-1504, 2018. (11/51959-0, 12/00111-4)

TORELLO, CRISTIANE OKUDA; SHIRAISHI, RODRIGO NAOTO; DELLA VIA, FERNANDA ISABEL; LOPES DE CASTRO, TAMARA CRISTINA; LONGHINI, ANA LEDA; SANTOS, IRENE; BOMBEIRO, ANDRE LUIS; ARAUJO SILVA, CLEIDE LUCIA; DE SOUZA QUEIROZ, MARY LUCI; REGO, EDUARDO MAGALHAES; et al. Reactive oxygen species production triggers green tea-induced anti-leukaemic effects on acute promyelocytic leukaemia model. Cancer Letters, v. 414, p. 116-126, FEB 1 2018. (11/51959-0, 14/08939-7)

MACHADO-NETO, JOAO AGOSTINHO; LAZARINI, MARIANA; FAVARO, PATRICIA; CAMPOS, PAULA DE MELO; SCOPIM-RIBEIRO, RENATA; FRANCHI JUNIOR, GILBERTO CARLOS; NOWILL, ALEXANDRE EDUARDO; MOURA LIMA, PAULO ROBERTO; COSTA, FERNANDO FERREIRA; BENICHOU, SERGE; et al. ANKHD1 silencing inhibits Stathmin 1 activity, cell proliferation and migration of leukemia cells. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1853, n. 3, p. 583-593, MAR 2015. (09/00268-8, 11/51959-0, 11/06840-5, 12/09982-8)

DE THOMAZ, A. A.; ALMEIDA, D. B.; PELEGATI, V. B.; CARVALHO, H. F.; MOREIRA, S. G. C.; BARBOSA, L. C.; CESAR, C. L.. The role of stress in CdTe quantum dot doped glasses. JOURNAL OF PHYSICS D-APPLIED PHYSICS, v. 49, n. 47, p. 1-5, NOV 1 2016. (05/51689-2, 11/51959-0)

NATAL, RODRIGO DE ANDRADE; PAIVA, GEISILENE R.; PELEGATI, VITOR B.; MARENCO, LUDWING; ALVARENGA, CESAR A.; VARGAS, RENATO F.; DERCHAIN, SOPHIE F.; SARIAN, LUIS O.; FRANCHET, CAMILLE; CESAR, CARLOS L.; et al. Exploring Collagen Parameters in Pure Special Types of Invasive Breast Cancer. SCIENTIFIC REPORTS, v. 9, MAY 22 2019. (11/51959-0)

MOREIRA, WENDEL LOPES; RANHA NEVES, ANTONIO ALVARO; GARBOS, MARTIN K.; EUSER, TIJMEN G.; CESAR, CARLOS LENZ. Expansion of arbitrary electromagnetic fields in terms of vector spherical wave functions. Optics Express, v. 24, n. 3, p. 2370-2382, FEB 8 2016. (05/51689-2, 11/51959-0)

PERICOLE, FERNANDO VIEIRA; LAZARINI, MARIANA; DE PAIVA, LUCIANA BUENO; SANTOS DUARTE, ADRIANA DA SILVA; VIEIRA FERRO, KARLA PRISCILA; NIEMANN, FERNANDA SOARES; ROVERSI, FERNANDA MARCONI; OLALLA SAAD, SARA TERESINHA. BRD4 Inhibition Enhances Azacitidine Efficacy in Acute Myeloid Leukemia and Myelodysplastic Syndromes. FRONTIERS IN ONCOLOGY, v. 9, JAN 29 2019. (11/51959-0)

BARBUTTI, ISABELLA; MACHADO-NETO, JOAO AGOSTINHO; ARFELLI, VANESSA CRISTINA; CAMPOS, PAULA DE MELO; TRAINA, FABIOLA; OLALLA SAAD, SARA TERESINHA; ARCHANGELO, LETICIA FROHLICH. The U2AF homology motif kinase 1 (UHMK1) is upregulated upon hematopoietic cell differentiation. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1864, n. 3, p. 959-966, MAR 2018. (11/51959-0, 14/01458-3)

BENITES, BRUNO DELTREGGIA; SANTOS DUARTE, ADRIANA DA SILVA; FIGUEIREDO LONGHINI, ANA LEDA; SANTOS, IRENE; ALVAREZ, MARISA CLAUDIA; DE MORAIS RIBEIRO, LIGIA NUNES; DE PAULA, ENEIDA; OLALLA SAAD, SARA TERESINHA. Exosomes in the serum of Acute Myeloid Leukemia patients induce dendritic cell tolerance: Implications for immunotherapy. Vaccine, v. 37, n. 11, p. 1377-1383, MAR 7 2019. (11/51959-0)

UTINO, FABIANE LEONEL; GARCIA, MARINA; NEVES FERREIRA VELHO, PAULO EDUARDO; ELOY DA COSTA FRANCA, ANDREA FERNANDES; STELINI, RAFAEL FANTELLI; PELEGATI, VITOR BIANCHIN; CESAR, CARLOS LENZ; DE SOUZA, ELEMIR MACEDO; CINTRA, MARIA LETICIA; DAMIANI, GISLAINE VIEIRA. Second-harmonic generation imaging analysis can help distinguish sarcoidosis from tuberculoid leprosy. Journal of Biomedical Optics, v. 23, n. 12, DEC 2018. (17/17149-8, 16/22927-7, 14/50938-8, 11/51959-0)

GALVAO, FABIO; ZANONI, CAMILA TATIANA; MOREIRA, MARCOS MELLO; PASCHOAL, ILMA APARECIDA; OLALLA SAAD, SARA TERESINHA. Effects of home-based inspiratory muscle training on sickle cell disease (SCD) patients. Hematology, Transfusion and Cell Therapy, v. 43, n. 4, p. 443-452, OCT-DEC 2021. (17/21801-2, 11/51959-0)

DOS SANTOS, ANDREY; CORDEIRO DANTAS, LARISSA ELIZABETH; TRAINA, FABIOLA; DE ALBUQUERQUE, DULCINEIA MARTINS; CHAIM, ELINTON ADAMI; SAAD, SARA T. OLALLA. Pyrimidine-5 `-nucleotidase Campinas, a new mutation (p.R56G) in the NT5C3 gene associated with pyrimidine-5 `-nucleotidase type I deficiency and influence of Gilbert's Syndrome on clinical expression. BLOOD CELLS MOLECULES AND DISEASES, v. 53, n. 4, p. 246-252, DEC 2014. (08/57895-1, 11/51959-0)

DELLA VIA, FERNANDA ISABEL; SHIRAISHI, RODRIGO NAOTO; SANTOS, IRENE; FERRO, KARLA PRISCILA; SALAZAR-TERREROS, MYRIAM JANETH; FRANCHI JUNIOR, GILBERTO CARLOS; REGO, EDUARDO MAGALHAES; OLALLA SAAD, SARA TERESINHA; TORELLO, CRISTIANE OKUDA. (-)-Epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and PIN1. SCIENTIFIC REPORTS, v. 11, n. 1, APR 27 2021. (17/21801-2, 11/51959-0)

COSTA MELO SVIDNICKI, MARIA CAROLINA; FERREIRA FILHO, MOISES ALVES; BRANDAO, MARCELO MENDES; DOS SANTOS, MARIELZA; DIAS, RENATA DE OLIVEIRA; TAVARES, RENATO SAMPAIO; ASSIS-MENDONCA, GUILHERME ROSSI; TRAINA, FABIOLA; OLALLA SAAD, SARA TERESINHA. New germline GATA1 variant in females with anemia and thrombocytopenia. BLOOD CELLS MOLECULES AND DISEASES, v. 88, MAY 2021. (17/21801-2, 15/18574-9, 11/51959-0)

ERMAKOV, VICTOR A.; JIMENEZ-VILLAR, ERNESTO; CLEMENTE DA SILVA FILHO, JOSE MARIA; YASSITEPE, EMRE; VARDHAN MOGILI, NAGA VISHNU; IIKAWA, FERNANDO; DE SA, GILBERTO FERNANDES; CESAR, CARLOS LENZ; MARQUEST, FRANCISCO CHAGAS. Size Control of Silver-Core/Silica-Shell Nanoparticles Fabricated by Laser-Ablation-Assisted Chemical Reduction. Langmuir, v. 33, n. 9, p. 2257-2262, MAR 7 2017. (05/51689-2, 13/26385-6, 11/51959-0, 12/10127-5)

DOS SANTOS, MOISES OLIVEIRA; LATRIVE, ANNE; AUGUSTO DE CASTRO, PEDRO ARTHUR; DE ROSSI, WAGNER; TENORIO ZORN, TELMA MARIA; SAMAD, RICARDO ELGUL; FREITAS, ANDERSON ZANARDI; CESAR, CARLOS LENZ; VIEIRA JUNIOR, NILSON DIAS; ZEZELL, DENISE MARIA. Multimodal evaluation of ultra-short laser pulses treatment for skin burn injuries. BIOMEDICAL OPTICS EXPRESS, v. 8, n. 3, p. 1575-1588, MAR 1 2017. (05/51689-2, 11/51959-0)

ERMAKOV, VIKTOR A.; CLEMENTE DA SILVA FILHO, JOSE MARIA; BONATO, LUIZ GUSTAVO; VARDHAN MOGILI, NAGA VISHNU; MONTORO, FABIANO EMMANUEL; IIKAWA, FERNANDO; NOGUEIRA, ANA FLAVIA; CESAR, CARLOS LENZ; JIMENEZ-VILLAR, ERNESTO; MARQUES, FRANCISCO CHAGAS. Three-Dimensional Superlattice of PbS Quantum Dots in Flakes. ACS OMEGA, v. 3, n. 2, p. 2027-2032, FEB 2018. (05/51689-2, 13/26385-6, 11/51959-0, 12/10127-5, 17/05854-9)

VIEIRA-DAMIANI, GISLAINE; LAGE, DENISE; CHRISTOFOLETTI DALDON, PATRICIA ERICA; TIBURCIO ALVES, CAROLINE ROMANELLI; CINTRA, MARIA LETICIA; METZE, KONRADIN; ADUR, JAVIER; PELEGATI, VITOR B.; CARVALHO, HERNANDES F.; CESAR, CARLOS LENZ. Idiopathic atrophoderma of Pasini and Pierini: A case study of collagen and elastin texture by multiphoton microscopy. JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, v. 77, n. 5, p. 930-937, NOV 2017. (11/51959-0)

PELEGATI, VITOR B.; KYOTOKU, BERNARDO B. C.; PADILHA, LAZARO A.; CESAR, CARLOS L.. Six-wave mixing coherent anti-Stokes Raman scattering microscopy. BIOMEDICAL OPTICS EXPRESS, v. 9, n. 5, p. 2407-2417, MAY 1 2018. (05/51689-2, 13/16911-2, 11/51959-0, 14/50938-8)

SCOPIM-RIBEIRO, RENATA; MACHADO-NETO, JOAO AGOSTINHO; CAMPOS, PAULA DE MELO; NIEMANN, FERNANDA SOARES; LORAND-METZE, IRENE; COSTA, FERNANDO FERREIRA; OLALLA SAAD, SARA TERESINHA; TRAINA, FABIOLA. Low Ten-eleven-translocation 2 (TET2) transcript level is independent of TET2 mutation in patients with myeloid neoplasms. DIAGNOSTIC PATHOLOGY, v. 11, MAR 16 2016. (11/51959-0, 12/09982-8, 11/15905-3)

BARBUTTI, ISABELLA; XAVIER-FERRUCIO, JULIANA M.; MACHADO-NETO, JOAO AGOSTINHO; RICON, LAUREMILIA; TRAINA, FABIOLA; BOHLANDER, STEFAN K.; OLALLA SAAD, SARA TERESINHA; ARCHANGELO, LETICIA FROHLICH. CATS (FAM64A) abnormal expression reduces clonogenicity of hematopoietic cells. ONCOTARGET, v. 7, n. 42, p. 68385-68396, OCT 18 2016. (11/51959-0, 11/18188-0)

MACHADO-NETO, JOAO AGOSTINHO; CAMPOS, PAULA DE MELO; FAVARO, PATRICIA; LAZARINI, MARIANA; SANTOS DUARTE, ADRIANA DA SILVA; LORAND-METZE, IRENE; COSTA, FERNANDO FERREIRA; OLALLA SAAD, SARA TERESINHA; TRAINA, FABIOLA. Stathmin 1 inhibition amplifies ruxolitinib-induced apoptosis in JAK2(V617F) cells. ONCOTARGET, v. 6, n. 30, p. 29573-29584, OCT 6 2015. (11/51959-0, 11/06840-5, 12/09982-8, 14/23092-0)

LIMA, KELI; RIBEIRO, DANIELA MARIA; CAMPOS, PAULA DE MELO; COSTA, FERNANDO FERREIRA; TRAINA, FABIOLA; OLALLA SAAD, SARA TERESINHA; SONATI, MARIA DE FATIMA; MACHADO-NETO, JOAO AGOSTINHO. Differential profile of PIP4K2A expression in hematological malignancies. BLOOD CELLS MOLECULES AND DISEASES, v. 55, n. 3, p. 228-235, OCT 2015. (11/51959-0, 14/00984-3)

MARENCO, LUDWING; CARMONA, HUMBERTO A.; CARDOSO, FELIPE MACIEL; ANDRADE, JR., JOSE S.; CESAR, CARLOS LENZ. Time evolution of the behaviour of Brazilian legislative Representatives using a complex network approach. PLoS One, v. 15, n. 2, FEB 5 2020. (16/00328-4, 11/51959-0)

SHIRAISHI, RODRIGO N.; BOMBEIRO, ANDRE L.; CASTRO, TAMARA C. L.; DELLA VIA, FERNANDA I.; SANTOS, IRENE; REGO, EDUARDO M.; SAAD, SARA T. O.; TORELLO, CRISTIANE O.. PML/RARa leukemia induced murine model for immunotherapy evaluation. TRANSPLANT IMMUNOLOGY, v. 81, p. 14-pg., 2023-08-26. (13/21539-5, 17/21801-2, 11/51959-0)

DOS SANTOS, ANDREY; CORDEIRO DANTAS, LARISSA ELIZABETH; TRAINA, FABIOLA; DE ALBUQUERQUE, DULCINEIA MARTINS; CHAIM, ELINTON ADAMI; SAAD, SARA T. OLALLA. Pyrimidine-5 '-nucleotidase Campinas, a new mutation (p.R56G) in the NT5C3 gene associated with pyrimidine-5 '-nucleotidase type I deficiency and influence of Gilbert's Syndrome on clinical expression. BLOOD CELLS MOLECULES AND DISEASES, v. 53, n. 4, p. 7-pg., 2014-12-01. (08/57895-1, 11/51959-0)

CALGAROTTO, ANDRANA K.; LONGHINI, ANA L.; PERICOLE DE SOUZA, FERNANDO V.; DUARTE, ADRIANA S. SANTOS; FERRO, KARLA P.; SANTOS, IRENE; MASO, VICTOR; OLALLA SAAD, SARA T.; TORELLO, CRISTIANE OKUDA. Immunomodulatory Effect of Green Tea Treatment in Combination with Low-dose Chemotherapy in Elderly Acute Myeloid Leukemia Patients with Myelodysplasia-related Changes. INTEGRATIVE CANCER THERAPIES, v. 20, p. 12-pg., 2021-03-01. (12/06675-7, 11/51959-0)