RESUMO
Although rare, CALM/AF10 is a chromosomal rearrangement found in immature T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia, and mixed phenotype acute leukemia of T/myeloid lineages with poor prognosis. Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). However, the relevance of CEBPA low expression for CALM/AF10 leukemogenesis has not yet been evaluated. We generated double mutant mice, which express the Lck-CALM/AF10 fusion gene and are haploinsufficient for the Cebpa gene. To characterize the hematopoiesis, we quantified hematopoietic stem cells, myeloid progenitor cells, megakaryocyte-erythrocyte progenitor cells, common myeloid progenitor cells, and granulocyte-macrophage progenitor cells. No significant difference was detected in any of the progenitor subsets. Finally, we tested if Cebpa haploinsufficiency would lead to the expansion of Mac-1+/B220+/c-Kit+ cells proposed as the CALM/AF10 leukemic progenitor. Less than 1% of bone marrow cells expressed Mac-1, B220, and c-Kit with no significant difference between groups. Our results showed that the reduction of Cebpa gene expression in Lck-CALM/AF10 mice did not affect their hematopoiesis or induce leukemia. Our data corroborated previous studies suggesting that the CALM/AF10 leukemia-initiating cells are early progenitors with lymphoid/myeloid differentiating potential.
Assuntos
Proteína alfa Estimuladora de Ligação a CCAAT/genética , Haploinsuficiência/genética , Hematopoese/genética , Leucemia Mieloide Aguda/genética , Doença Aguda , Animais , Citometria de Fluxo , Genótipo , Camundongos , Camundongos Transgênicos , Fenótipo , Fatores de Transcrição/genética , Translocação Genética/genéticaRESUMO
Although rare, CALM/AF10 is a chromosomal rearrangement found in immature T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia, and mixed phenotype acute leukemia of T/myeloid lineages with poor prognosis. Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). However, the relevance of CEBPA low expression for CALM/AF10 leukemogenesis has not yet been evaluated. We generated double mutant mice, which express the Lck-CALM/AF10 fusion gene and are haploinsufficient for the Cebpa gene. To characterize the hematopoiesis, we quantified hematopoietic stem cells, myeloid progenitor cells, megakaryocyte-erythrocyte progenitor cells, common myeloid progenitor cells, and granulocyte-macrophage progenitor cells. No significant difference was detected in any of the progenitor subsets. Finally, we tested if Cebpa haploinsufficiency would lead to the expansion of Mac-1+/B220+/c-Kit+ cells proposed as the CALM/AF10 leukemic progenitor. Less than 1% of bone marrow cells expressed Mac-1, B220, and c-Kit with no significant difference between groups. Our results showed that the reduction of Cebpa gene expression in Lck-CALM/AF10 mice did not affect their hematopoiesis or induce leukemia. Our data corroborated previous studies suggesting that the CALM/AF10 leukemia-initiating cells are early progenitors with lymphoid/myeloid differentiating potential.
Assuntos
Animais , Coelhos , Leucemia Mieloide Aguda/genética , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Haploinsuficiência/genética , Hematopoese/genética , Fenótipo , Fatores de Transcrição/genética , Translocação Genética/genética , Camundongos Transgênicos , Doença Aguda , Citometria de Fluxo , GenótipoRESUMO
OBJECTIVE: To analyze the expression and distribution patterns of mature dendritic cells (mDCs) and immature DCs (imDCs) in radicular cysts (RCs), dentigerous cysts (DtCs), and keratocystic odontogenic tumors (KCOTs). MATERIALS AND METHODS: Forty-nine odontogenic cystic lesions (OCLs) (RCs, n = 20; DtCs, n = 15; KCOTs, n = 14) were assessed using the following markers: S100, CD1a and CD207 for imDCs; and CD83 for mDCs. RESULTS: Almost all cases were S100, CD1a, and CD207 positive, whereas 63% were CD83 positive. RCs presented greater number of immunostained cells, followed by DtCs, and KCOTs. The number of S100+ cells was greater than both CD1a+ and CD207+ cells (P < 0.001), which showed approximately similar amounts, followed by lower number of CD83+ cells (P < 0.001) in each OCL type. Different from S100+ cells, both CD1a+ and CD207+ cells on the epithelium (P < 0.05) and CD83+ cells on the capsule (P < 0.05) were preferentially observed. In RCs, significant correlation was found between the thickness epithelium with S100+ and CD1a+ cells, and between the degree of inflammation with CD83+ cells. CONCLUSIONS: Dendritic cell populations in OCLs can be phenotypically heterogeneous, and it could represent distinct lineages and/or functional stages. It is suggested that besides DC-mediated immune cell interactions, DC-mediated tissue differentiation and maintenance in OCLs should also be considered.
