AIM To evaluate the importance of the CD34+CD38-cell population when compared to the CD34+CD38+/low and CD34+CD38+/high leukemic cell sub-populations and to determine its correlations with leukemia characteristics and...AIM To evaluate the importance of the CD34+CD38-cell population when compared to the CD34+CD38+/low and CD34+CD38+/high leukemic cell sub-populations and to determine its correlations with leukemia characteristics and known prognostic factors, as well as with response to therapy and survival.METHODS Two hundred bone marrow samples were obtained at diagnosis from 200 consecutive patients with newly diagnosed acute myeloid leukemia(AML) were studied between September 2008 and December 2010 at our Institution(Hematology Department, Lyon, France). The CD34/CD38 cell profile was analyzed by multiparameter flowcytometry approach using 8 C panels and FACS CANTO and Diva software(BD Bioscience).RESULTS We analyzed CD34 and CD38 expression in bone marrow samples of 200 AML patients at diagnosis, and investigated the prognostic value of the most immature CD34+CD38-population. Using a cut-off value of 1% of CD34+CD38-from total "bulk leukemic cells" we found that a high(> 1%) level of CD34+CD38-blasts at diagnosis was correlated with advanced age, adverse cytogenetics as well as with a lower rate of complete response after induction and shorter disease-free survival. In a multivariate analysis considering age, leukocytosis, the % of CD34+ blasts cells and the standardized cytogenetic and molecular risk subgroups, a percentage of CD34+CD38-leukemic cells > 1% was an independent predictor of DFS [HR = 2.8(1.02-7.73), P = 0.04] and OS [HR = 2.65(1.09-6.43), P = 0.03].CONCLUSION Taken together, these results show that a CD34/CD38 "backbone" for leukemic cell analysis by multicolour flowcytometry at diagnosis provides useful prognostic information.展开更多
T cell development proceeds un der the in fluence of a n etwork of transcription factors(TFs).The precise role of Zeb1,a member of this network,remains unclear.Here,we report that Zeb1 expression is induced early duri...T cell development proceeds un der the in fluence of a n etwork of transcription factors(TFs).The precise role of Zeb1,a member of this network,remains unclear.Here,we report that Zeb1 expression is induced early during T cell development in CD4^(-)CD8^(-)double-negative(DN)stage 2(DN2).Zeb1 expression was further increased in the CD4^(+)CD8^(+)double-positive(DP)stage before decreasing in more mature T cell subsets.We performed an exhaustive characterization of T cells in Cellophane mice that bear Zeb 7 hypomorphic mutations.The Zebl mutation profoundly affected all thymic subsets,especially DN2 and DP cells.Zeb1 promoted the survival and proliferation of both cell populations in a cell-intrinsic manner.In the periphery of Cellophane mice,the number of conventional T cells was near normal,but invariant NKT cells,NK1.1^(+)γδ T cells and Ly49^(+)CD8 T cells were virtually absent.This suggested that Zebl regulates the development of unconventional T cell types from DP progenitors.A transcriptomic analysis of WT and Cellophane DP cells revealed that Zebl regulated the expression of multiple genes involved in the cell cycle and TCR sign aling,which possibly occurred in cooperation with Tcf1 and Heb.In deed,Cellophane DP cells displayed stron ger signaling than WT DP cells upon TCR engagement in terms of the calcium respons巳phosphorylation events,and expression of early genes.Thus,Zebl is a key regulator of the cell cycle and TCR signaling during thymic T cell development.We propose that thymocyte selection is perturbed in Zeb7-mutated mice in a way that does not allow the survival of unconventional T cell subsets.展开更多
文摘AIM To evaluate the importance of the CD34+CD38-cell population when compared to the CD34+CD38+/low and CD34+CD38+/high leukemic cell sub-populations and to determine its correlations with leukemia characteristics and known prognostic factors, as well as with response to therapy and survival.METHODS Two hundred bone marrow samples were obtained at diagnosis from 200 consecutive patients with newly diagnosed acute myeloid leukemia(AML) were studied between September 2008 and December 2010 at our Institution(Hematology Department, Lyon, France). The CD34/CD38 cell profile was analyzed by multiparameter flowcytometry approach using 8 C panels and FACS CANTO and Diva software(BD Bioscience).RESULTS We analyzed CD34 and CD38 expression in bone marrow samples of 200 AML patients at diagnosis, and investigated the prognostic value of the most immature CD34+CD38-population. Using a cut-off value of 1% of CD34+CD38-from total "bulk leukemic cells" we found that a high(> 1%) level of CD34+CD38-blasts at diagnosis was correlated with advanced age, adverse cytogenetics as well as with a lower rate of complete response after induction and shorter disease-free survival. In a multivariate analysis considering age, leukocytosis, the % of CD34+ blasts cells and the standardized cytogenetic and molecular risk subgroups, a percentage of CD34+CD38-leukemic cells > 1% was an independent predictor of DFS [HR = 2.8(1.02-7.73), P = 0.04] and OS [HR = 2.65(1.09-6.43), P = 0.03].CONCLUSION Taken together, these results show that a CD34/CD38 "backbone" for leukemic cell analysis by multicolour flowcytometry at diagnosis provides useful prognostic information.
基金The TW lab is supported by the Agence Nationale de la Recherche(ANR GAMBLER to TW and ANR JC BaNK to AM)the Institut National du Cancer and receives institutional grants from the Institut National de la Sante et de la Recherche Medicale(INSERM)+4 种基金Centre National de la Recherche Scientifique(CNRS)Universite Claude Bernard Lyon and ENS de Lyonthe Joint Research Institute for Science and Society(JORISS)JZ is the recipient of a fellowship from the China Scholarship Council(CSC)RS and YGH were funded by an FRM grant(AJE20161236686)to YGH.
文摘T cell development proceeds un der the in fluence of a n etwork of transcription factors(TFs).The precise role of Zeb1,a member of this network,remains unclear.Here,we report that Zeb1 expression is induced early during T cell development in CD4^(-)CD8^(-)double-negative(DN)stage 2(DN2).Zeb1 expression was further increased in the CD4^(+)CD8^(+)double-positive(DP)stage before decreasing in more mature T cell subsets.We performed an exhaustive characterization of T cells in Cellophane mice that bear Zeb 7 hypomorphic mutations.The Zebl mutation profoundly affected all thymic subsets,especially DN2 and DP cells.Zeb1 promoted the survival and proliferation of both cell populations in a cell-intrinsic manner.In the periphery of Cellophane mice,the number of conventional T cells was near normal,but invariant NKT cells,NK1.1^(+)γδ T cells and Ly49^(+)CD8 T cells were virtually absent.This suggested that Zebl regulates the development of unconventional T cell types from DP progenitors.A transcriptomic analysis of WT and Cellophane DP cells revealed that Zebl regulated the expression of multiple genes involved in the cell cycle and TCR sign aling,which possibly occurred in cooperation with Tcf1 and Heb.In deed,Cellophane DP cells displayed stron ger signaling than WT DP cells upon TCR engagement in terms of the calcium respons巳phosphorylation events,and expression of early genes.Thus,Zebl is a key regulator of the cell cycle and TCR signaling during thymic T cell development.We propose that thymocyte selection is perturbed in Zeb7-mutated mice in a way that does not allow the survival of unconventional T cell subsets.
