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Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies

Signal Transduction and Targeted Therapy 2021年第2期6卷 409-424页

作者： Zi Wang Pan Wang Yanan Li Hongling Peng Yu Zhu narla mohandas Jing Liu Department of Hematology Istitute of Molecular HematologyThe Second Xiangya HospitalCentral South University41001 ChangShaHunanChina Molecular Biology Research Center and Hunan Province Key Laboratory of Basic and Applied Hematology School of Life SciencesCentral South University410078 ChangshaHunanChina Red Cell Physiology Laboratory New York Blood CenterNew YorkNYUSA

Hematopoiesis requires finely tuned regulation of gene expression at each stage of development.The regulation of gene transcription involves not only individual transcription factors(TFs)but also transcription complexes(TCs)composed of transcription factor(s)and multisubunit cofactors.In their normal compositions,TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis.The integration of posttranslational and conformational modifcations in the chromatin landscape,nucleosomes,histones and interacting components via the cofactor-TF interplay is critical to optimal TF activity.Mutations or translocations of cofactor genes are expected to alter cofactor-TF interactions,which may be causative for the pathogenesis of various hematologic disorders.Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy.In this review,we summarize the current knowledge regarding the models and functions of cofactor-TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies.This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.

关键词： hematopoiesis cofactor landscape

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Is the erythropoietin receptor the key to the identification of the central macrophage in erythroblastic islands?

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Blood Science 2020年第1期2卷 38-39页

作者： Lionel Blanc narla mohandas Laboratory of Developmental Erythropoiesis Department of Molecular Medicine and PediatricsThe Feinstein Institute for Medical ResearchZucker School of Medicine at Hofstra/NorthwellManhassetNY 11030USA Red Cell Physiology Laboratory New York Blood CenterNew YorkNY 10065USA

Erythroblastic islands(EBI)are niches for mammalian erythropoiesis.1 They were first identified in 1958 by Marcel Bessis and consist of a group of differentiating erythroblasts surrounding a central macrophage.2 Over the years,a lot of attention has been paid to understand the role of the central macrophage in regulating the differentiation of the maturing erythroblasts within these islands and in defining the surface proteins thatmediate the interaction between the erythroblasts and the centralmacrophage.3–14While some progress has beenmade in these areas of investigation,the definitive identity of this central macrophage and its function is yet to be fully characterized.

关键词： macrophage. blastic interaction

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Multiple STEAP3 loss-of-function heterozygous mutations identified in the Chinese population with no phenotypic red cell alterations

Multiple STEAP3 loss-of-function heterozygous mutations iden...

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第十四次全国医学遗传学学术会议

作者： Dun Liu Sheng Yi Xinhua Zhang Ping Fang Chenguang Zheng Li Lin Ren Cai Yuhua Ye Yuqiu Zhou Yunhao Liang Feng Cheng Xuelian Zhang Wanjun Zhou narla mohandas Xiuli An Xiangmin Xu Department of Medical Genetics School of Basic Medical SciencesSouthern Medical University Department of Hematology 303rd Hospital of the People's Liberation Army Prenatal Diagnostic Center Guangxi Zhuang Autonomous Region Women and Children Care Hospital Department of Birth Health and Heredity Liuzhou Women and Children Care Hospital Department of Birth Health and Heredity Zhuhai Women and Children Care Hospital Red Cell Physiology Laboratory New York Blood Center

A ferrireductase encoded by six-transmembrane epithelial antigen of the prostate3(STEAP3)has been implicated in the regulation of iron homeostasis.STEAP3 null mice exhibit congenital hypochromic anemia and in a rare case of human anemia has been recently reported due to STEAP3 mutations.However,there is little information on the prevelance of STEAP3 mutations in humans and their physiological consequences.Molecular analysis in a total of 2338 Chinese random individuals showed mutations in STEAP3,for a prevalence of 5.3%.We characterized the spectrum of these STEAP3mutations and identified sixteen functional variants.The three most common mutations,p.Cys261Ter,p.Arg290His and p.Gly51Asp,accounted for 72.6%of the total.Although the heterozygous STEAP3 mutations resulted in either moderate or severe reductions in enzyme activities in vitro,they had little or no effects on red cell parameters.Furthermore,when we scanned for STEAP3 mutations in 867 subjects with-thalassemia,we were unable to document the adverse effects of STEAP3 mutations on the-thalassemia phenotypes.Our findings imply that heterozygous STEAP3 mutations are not deleterious in humans and suggest that lack of phenotypic changes is due to the presence of sufficient residual STEAP3 activity or the presence of other ferrireductases in erythroid cells.

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