BACKGROUND Acute leukemia in newborns is also known as neonatal or congenital leukemia(CL)and is a rare disease with an incidence rate of 1-5 per 1000000 live births.After birth,infants with CL exhibit infiltrative cu...BACKGROUND Acute leukemia in newborns is also known as neonatal or congenital leukemia(CL)and is a rare disease with an incidence rate of 1-5 per 1000000 live births.After birth,infants with CL exhibit infiltrative cutaneous nodules,hepatosplenomegaly,thrombocytopenia,and immature leukocytes in the peripheral blood.These symptoms are frequently accompanied by congenital abnormalities including trisomy 21,trisomy 9,trisomy 13,or Turner syndrome.Despite significant advances in disease management,the survival rate is approximately 25%at 2 years.CASE SUMMARY Here,we document a case of trisomy 21-related acute myeloid leukemia(AML)in a female neonate.The baby was sent to the neonatal intensive care unit because of anorexia,poor responsiveness,and respiratory distress.She was diagnosed with AML based on bone marrow aspiration and immunophenotyping.Genetic sequencing identified a mutation in the GATA1 gene.After receiving the diagnosis,the parents decided against medical care for their child,and the baby died at home on day 9 after birth.CONCLUSIONS The newborn infant was diagnosed with trisomy 21-related AML.Genetic sequencing identified a mutation in the GATA1 gene.The parents abandoned medical treatment for their infant after receiving the diagnosis,and the infant died at home on the 9th day after birth.展开更多
One case of acute megakaryoblastic leukemia （AMKL） with trisomy 21,trisomy 14 and unmutated GATA1 gene in a phenotypically normal girl was reported.The patient experienced transient myelodysplasia before the onset o...One case of acute megakaryoblastic leukemia （AMKL） with trisomy 21,trisomy 14 and unmutated GATA1 gene in a phenotypically normal girl was reported.The patient experienced transient myelodysplasia before the onset of AMKL.The bone marrow blasts manifested typical morphology of megakaryoblast both by the May-Giemsa staining and under the electronic microscopy.Leukemic cells were positive for CD13,CD33,CD117,CD56,CD38,CD41 and CD61 in flow cytometry analysis.Cytogenetic study showed karyotype of 48,XX,＋14,＋21 in 40% metaphases.Known mutations of GATA1 gene in Down syndrome or acquired trisomy 21 were not detected in this case.展开更多
OBJECTIVE: To further characterize the differentiation inducing properties of EDRF1 and demonstrate its functional pathway involved in regulation of globin gene expression. METHODS: By transfecting EDRF1 sense and ant...OBJECTIVE: To further characterize the differentiation inducing properties of EDRF1 and demonstrate its functional pathway involved in regulation of globin gene expression. METHODS: By transfecting EDRF1 sense and antisense constructs into HEL cells, we identified the expression of globin and erythropoietin receptor genes by Northern blot analysis. RT-PCR and EMSA (electrophoresis mobility shift assay) were performed to monitor the expression and DNA-binding activity of erythroid specific transcription factors GATA-1 and NF-E2. RESULTS: It was shown that when EDRF1 was overexpressed, production of alpha-globin increased. In antisense EDRF1, overexpression of HEL cells, significant loss of alpha-, gamma-globin mRNA synthesis was observed. The transcription of endogenous GATA-1 and NF-E2 mRNA expression were maintained at the same levels compared with control experiments. However, the transcription activity of GATA-1 was severely impaired. Expression of erythropoietin receptor gene was not influenced by EDRF1 gene overexpression. CONCLUSION: The results suggested that EDRF1 regulated alpha- and gamma-globin gene synthesis by modulating DNA-binding activity of GATA-1 transcription factor.展开更多
EAF1 and EAF2,the eleven-nineteen lysine-rich leukemia(ELL)-associated factors which can assemble to the super elongation complex(AFF1/4,AF9/ENL,ELL,and P-TEFb),are reported to participate in RNA polymeraseⅡto active...EAF1 and EAF2,the eleven-nineteen lysine-rich leukemia(ELL)-associated factors which can assemble to the super elongation complex(AFF1/4,AF9/ENL,ELL,and P-TEFb),are reported to participate in RNA polymeraseⅡto actively regulate a variety of biological processes,including leukemia and embryogenesis,but whether and how EAF1/2 function in hematopoietic system related hypoxia tolerance during embryogenesis remains unclear.Here,we unveiled that deletion of EAF1/2(eaf1^(-/-)and eaf2^(-/-))caused reduction in hypoxia tolerance in zebrafish,leading to reduced erythropoiesis during hematopoietic processes.Meanwhile,eaf1^(-/-)and eaf2^(-/-)mutants showed significant reduc-tion in the expression of key transcriptional regulators scl,lmo2,and gata1a in erythropoiesis at both 24 h post fertilization(hpf)and 72 hpf,with gata1a downregulated while scl and lmo2 upregulated at 14 hpf.Mechanistically,eaf1^(-/-)and eaf2^(-/-)mutants exhibited significant changes in the expression of epigenetic modified histones,with a significant increase in the binding enrichment of modified histone H3K27me3 in gata1a promoter rather than scl and lmo2 promoters.Additionally,eaf1^(-/-)and eaf2^(-/-)mutants exhibited a dynamic expression of canonical WNT/β-catenin signaling during erythropoiesis,with significant reduction in p-β-Catenin level and in the binding enrichment of both scl and lmo2 promoters with the WNT transcriptional factor TCF4 at 24 hpf.These findings demonstrate an important role of Eaf1/2 in erythropoiesis in zebrafish and may have shed some light on regeneration medicine for anemia and related diseases and on molecular basis for fish economic or productive traits,such as growth,disease resistance,hypoxia tolerance,and so on.展开更多
基金Supported by Project of Regional Science Foundation of National Natural Science Foundation,No.82060033Project of Scientific and Technological Innovation Talent Team in Guizhou Province,No.CXTD[2021]002.
文摘BACKGROUND Acute leukemia in newborns is also known as neonatal or congenital leukemia(CL)and is a rare disease with an incidence rate of 1-5 per 1000000 live births.After birth,infants with CL exhibit infiltrative cutaneous nodules,hepatosplenomegaly,thrombocytopenia,and immature leukocytes in the peripheral blood.These symptoms are frequently accompanied by congenital abnormalities including trisomy 21,trisomy 9,trisomy 13,or Turner syndrome.Despite significant advances in disease management,the survival rate is approximately 25%at 2 years.CASE SUMMARY Here,we document a case of trisomy 21-related acute myeloid leukemia(AML)in a female neonate.The baby was sent to the neonatal intensive care unit because of anorexia,poor responsiveness,and respiratory distress.She was diagnosed with AML based on bone marrow aspiration and immunophenotyping.Genetic sequencing identified a mutation in the GATA1 gene.After receiving the diagnosis,the parents decided against medical care for their child,and the baby died at home on day 9 after birth.CONCLUSIONS The newborn infant was diagnosed with trisomy 21-related AML.Genetic sequencing identified a mutation in the GATA1 gene.The parents abandoned medical treatment for their infant after receiving the diagnosis,and the infant died at home on the 9th day after birth.
文摘One case of acute megakaryoblastic leukemia （AMKL） with trisomy 21,trisomy 14 and unmutated GATA1 gene in a phenotypically normal girl was reported.The patient experienced transient myelodysplasia before the onset of AMKL.The bone marrow blasts manifested typical morphology of megakaryoblast both by the May-Giemsa staining and under the electronic microscopy.Leukemic cells were positive for CD13,CD33,CD117,CD56,CD38,CD41 and CD61 in flow cytometry analysis.Cytogenetic study showed karyotype of 48,XX,＋14,＋21 in 40% metaphases.Known mutations of GATA1 gene in Down syndrome or acquired trisomy 21 were not detected in this case.
文摘OBJECTIVE: To further characterize the differentiation inducing properties of EDRF1 and demonstrate its functional pathway involved in regulation of globin gene expression. METHODS: By transfecting EDRF1 sense and antisense constructs into HEL cells, we identified the expression of globin and erythropoietin receptor genes by Northern blot analysis. RT-PCR and EMSA (electrophoresis mobility shift assay) were performed to monitor the expression and DNA-binding activity of erythroid specific transcription factors GATA-1 and NF-E2. RESULTS: It was shown that when EDRF1 was overexpressed, production of alpha-globin increased. In antisense EDRF1, overexpression of HEL cells, significant loss of alpha-, gamma-globin mRNA synthesis was observed. The transcription of endogenous GATA-1 and NF-E2 mRNA expression were maintained at the same levels compared with control experiments. However, the transcription activity of GATA-1 was severely impaired. Expression of erythropoietin receptor gene was not influenced by EDRF1 gene overexpression. CONCLUSION: The results suggested that EDRF1 regulated alpha- and gamma-globin gene synthesis by modulating DNA-binding activity of GATA-1 transcription factor.
基金supported by the Nation Natural Science Foundation of China(Program No.32070807)by the National Key R&D Program of China(2018YFD0900101)by the project 2020SKLBC-KF06 of State Key Laboratory of Biocontrol.
文摘EAF1 and EAF2,the eleven-nineteen lysine-rich leukemia(ELL)-associated factors which can assemble to the super elongation complex(AFF1/4,AF9/ENL,ELL,and P-TEFb),are reported to participate in RNA polymeraseⅡto actively regulate a variety of biological processes,including leukemia and embryogenesis,but whether and how EAF1/2 function in hematopoietic system related hypoxia tolerance during embryogenesis remains unclear.Here,we unveiled that deletion of EAF1/2(eaf1^(-/-)and eaf2^(-/-))caused reduction in hypoxia tolerance in zebrafish,leading to reduced erythropoiesis during hematopoietic processes.Meanwhile,eaf1^(-/-)and eaf2^(-/-)mutants showed significant reduc-tion in the expression of key transcriptional regulators scl,lmo2,and gata1a in erythropoiesis at both 24 h post fertilization(hpf)and 72 hpf,with gata1a downregulated while scl and lmo2 upregulated at 14 hpf.Mechanistically,eaf1^(-/-)and eaf2^(-/-)mutants exhibited significant changes in the expression of epigenetic modified histones,with a significant increase in the binding enrichment of modified histone H3K27me3 in gata1a promoter rather than scl and lmo2 promoters.Additionally,eaf1^(-/-)and eaf2^(-/-)mutants exhibited a dynamic expression of canonical WNT/β-catenin signaling during erythropoiesis,with significant reduction in p-β-Catenin level and in the binding enrichment of both scl and lmo2 promoters with the WNT transcriptional factor TCF4 at 24 hpf.These findings demonstrate an important role of Eaf1/2 in erythropoiesis in zebrafish and may have shed some light on regeneration medicine for anemia and related diseases and on molecular basis for fish economic or productive traits,such as growth,disease resistance,hypoxia tolerance,and so on.
