Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Google Scholar, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Identification of a myeloid committed progenitor as the cancer-initiating cell in acute promyelocytic leukemia

Texto completo
Autor(es):
Mostrar menos -
Guibal, Florence C. [1, 2] ; Alberich-Jorda, Meritxell [1, 2] ; Hirai, Hideyo [1, 2] ; Ebralidze, Alexander [1, 2] ; Levantini, Elena [1, 2] ; Di Ruscio, Annalisa [1, 2] ; Zhang, Pu [1, 2] ; Santana-Lemos, Barbara A. [3] ; Neuberg, Donna [4] ; Wagers, Amy J. [1, 5] ; Rego, Eduardo M. [3] ; Tenen, Daniel G. [1, 2, 6]
Número total de Autores: 12
Afiliação do(s) autor(es):
[1] Harvard Stem Cell Inst, Boston, MA - USA
[2] Harvard Univ, Ctr Life Sci, Sch Med, Boston, MA 02115 - USA
[3] Univ Sao Paulo, Div Hematol, Dept Internal Med, Med Sch Ribeirao Preto, Ctr Cell Based Therapy, Sao Paulo - Brazil
[4] Dana Farber Canc Inst, Boston, MA 02115 - USA
[5] Harvard Univ, Sect Dev & Stem Cell Biol, Joslin Diabet Ctr, Dept Stem Cell & Regenerat Biol, Boston, MA 02115 - USA
[6] Natl Univ Singapore, Canc Sci Inst, Singapore 117548 - Singapore
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: Blood; v. 114, n. 27, p. 5415-5425, 2009.
Citações Web of Science: 94
Resumo

Acute promyelocytic leukemia (APL) is characterized by a block in differentiation and accumulation of promyelocytes in the bone marrow and blood. The majority of APL patients harbor the t(15: 17) translocation leading to expression of the fusion protein promyelocytic-retinoic acid receptor alpha. Treatment with retinoic acid leads to degradation of promyelocytic-retinoic acid receptor alpha protein and disappearance of leukemic cells; however, 30% of APL patients relapse after treatment. One potential mechanism for relapse is the persistence of cancer "stem" cells in hematopoietic organs after treatment. Using a novel sorting strategy we developed to isolate murine myeloid cells at distinct stages of differentiation, we identified a population of committed myeloid cells (CD34(+), c-kit(+), Fc gamma RIII/II+, Gr1(int)) that accumulates in the spleen and bone marrow in a murine model of APL. We observed that these cells are capable of efficiently generating leukemia in recipient mice, demonstrating that this population represents the APL cancer-initiating cell. These cells down-regulate the transcription factor CCAAT/enhancer binding protein alpha (C/EBP alpha) possibly through a methylation-dependent mechanism, indicating that C/EBP alpha deregulation contributes to transformation of APL cancer-initiating cells. Our findings provide further understanding of the biology of APL by demonstrating that a committed transformed progenitor can initiate and propagate the disease. (Blood. 2009; 114: 5415-5425) (AU)

Processo FAPESP: 01/07974-3 - Determinação do efeito da inativação do gene proteína ligante do enhancer CCAAT (C/EBPa) na hematopoese de animais transgênicos PML-RARa
Beneficiário:Barbara Amélia Aparecida Santana Lemos
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 01/08693-8 - Determinação do efeito da inativação do gene da proteína ligante do enhancer CCAAT (C/EBPa) na hematopoese de animais transgênicos PML-RARa
Beneficiário:Eduardo Magalhães Rego
Modalidade de apoio: Auxílio à Pesquisa - Regular