This SuperSeries is composed of the SubSeries listed below.
Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis.
Specimen part, Disease, Disease stage
View SamplesPhiladelphia-like B-cell precursor acute lymphoblastic leukemia (Ph-like ALL) is characterized by distinct genetic alterations and inferior prognosis in children and younger adults. The purpose of this study was the genetic and clinical characterization of Ph-like ALL in adults. Among 207 adult B-cell precursor ALL patients, 26 (13%) were classified as Ph-like using Affymetrix microarrays. The incidence of this subtype was 25% among 105 B-cell precursor ALL patients negative for BCR-ABL1 and MLL-translocations (B-other). All patients with IgH-CRLF2 translocation (38% vs 0%; p=0.002) or mutations in JAK2 (44% vs. 0%; p<0.001) were exclusively found in the Ph-like subgroup. Clinical and outcome analyses were restricted to patients treated within GMALL trials 06/99 and 07/03 (n=107). The complete remission (CR) rate after induction was 100% for Ph-like (n=19) and B-other patients (n=40). After induction, significantly fewer Ph-like patients reached molecular CR (33% vs 79%; p=0.01). At 5 years, the Ph-like ALL subgroup had a lower probability of continuous CR (24% vs 62%; p<0.001) and overall survival (22% vs 64%; p=0.006) compared to B-other ALL patients. Subsequent analysis led to a clinically applicable algorithm identifying this patient subset with a specificity of 100%. Our study is the first to demonstrate that the profile of genetic events in adult Ph-like ALL resembles pediatric Ph-like ALL and differs from B-other ALL. The Ph-like phenotype associates with inferior outcomes in intensively treated adult ALL patients. Ph-like adult ALL should be recognized as a distinct, high-risk entity and further research on improved diagnostic and therapeutic approaches is needed.
Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis.
Specimen part, Disease, Disease stage
View SamplesPhiladelphia-like B-cell precursor acute lymphoblastic leukemia (Ph-like ALL) is characterized by distinct genetic alterations and inferior prognosis in children and younger adults. The purpose of this study was the genetic and clinical characterization of Ph-like ALL in adults. Among 207 adult B-cell precursor ALL patients, 26 (13%) were classified as Ph-like using Affymetrix microarrays. The incidence of this subtype was 25% among 105 B-cell precursor ALL patients negative for BCR-ABL1 and MLL-translocations (B-other). All patients with IgH-CRLF2 translocation (38% vs 0%; p=0.002) or mutations in JAK2 (44% vs. 0%; p<0.001) were exclusively found in the Ph-like subgroup. Clinical and outcome analyses were restricted to patients treated within GMALL trials 06/99 and 07/03 (n=107). The complete remission (CR) rate after induction was 100% for Ph-like (n=19) and B-other patients (n=40). After induction, significantly fewer Ph-like patients reached molecular CR (33% vs 79%; p=0.01). At 5 years, the Ph-like ALL subgroup had a lower probability of continuous CR (24% vs 62%; p<0.001) and overall survival (22% vs 64%; p=0.006) compared to B-other ALL patients. Subsequent analysis led to a clinically applicable algorithm identifying this patient subset with a specificity of 100%. Our study is the first to demonstrate that the profile of genetic events in adult Ph-like ALL resembles pediatric Ph-like ALL and differs from B-other ALL. The Ph-like phenotype associates with inferior outcomes in intensively treated adult ALL patients. Ph-like adult ALL should be recognized as a distinct, high-risk entity and further research on improved diagnostic and therapeutic approaches is needed.
Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis.
Specimen part, Disease, Disease stage
View SamplesPhiladelphia-like B-cell precursor acute lymphoblastic leukemia (Ph-like ALL) is characterized by distinct genetic alterations and inferior prognosis in children and younger adults. The purpose of this study was the genetic and clinical characterization of Ph-like ALL in adults. Among 207 adult B-cell precursor ALL patients, 26 (13%) were classified as Ph-like using Affymetrix microarrays. The incidence of this subtype was 25% among 105 B-cell precursor ALL patients negative for BCR-ABL1 and MLL-translocations (B-other). All patients with IgH-CRLF2 translocation (38% vs 0%; p=0.002) or mutations in JAK2 (44% vs. 0%; p<0.001) were exclusively found in the Ph-like subgroup. Clinical and outcome analyses were restricted to patients treated within GMALL trials 06/99 and 07/03 (n=107). The complete remission (CR) rate after induction was 100% for Ph-like (n=19) and B-other patients (n=40). After induction, significantly fewer Ph-like patients reached molecular CR (33% vs 79%; p=0.01). At 5 years, the Ph-like ALL subgroup had a lower probability of continuous CR (24% vs 62%; p<0.001) and overall survival (22% vs 64%; p=0.006) compared to B-other ALL patients. Subsequent analysis led to a clinically applicable algorithm identifying this patient subset with a specificity of 100%. Our study is the first to demonstrate that the profile of genetic events in adult Ph-like ALL resembles pediatric Ph-like ALL and differs from B-other ALL. The Ph-like phenotype associates with inferior outcomes in intensively treated adult ALL patients. Ph-like adult ALL should be recognized as a distinct, high-risk entity and further research on improved diagnostic and therapeutic approaches is needed.
Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis.
Specimen part, Disease, Disease stage
View SamplesThe histone variant H3.3 is incorporated in a replication-independent manner at heterochromatic regions by the ATRX-DAXX histone chaperone complex. Here, we present a high-resolution x-ray crystal structure of an interaction surface between ATRX and DAXX. We used single amino acid substitutions in DAXX that abrogate formation of the complex to explore ATRX-dependent and -independent functions of DAXX. We found that the repression of specific murine endogenous retroviruses is dependent on DAXX, but not on ATRX. In support, we reveal the existence of two biochemically distinct DAXX-containing complexes: The ATRX-DAXX complex involved in gene repression and telomere chromatin structure, and a DAXX-SETDB1-KAP1-HDAC1 complex that represses endogenous retroviruses independently of ATRX and H3.3 incorporation into chromatin. We found that histone H3.3 stabilizes DAXX protein levels and affects DAXX-regulated genes independently of its incorporation into nucleosomes. Our findings represent the first description of a nucleosome-independent function for the H3.3 histone variant. Overall design: RNA-seq analysis of five embryonic stem cell lines in duplicate (Daxx-/- mESC, Daxx-/- mESC rescued with Daxx WT, H3.3 KO mESC, H3.3 KO mESC rescued with H3.3 WT and H3.3 L126A-L130A mutant)
Structural and mechanistic insights into ATRX-dependent and -independent functions of the histone chaperone DAXX.
Specimen part, Cell line, Subject
View SamplesInducible co-stimulator (ICOS) interaction with its ligand (ICOSL) is involved in several T cell effector functions. While blockade of ICOS:ICOSL interaction in chronic graft versus host disease (GVHD) seems benefi cial, results for acute GVHD remain controversial. To further elucidate its role in acute GVHD, C57BL / 6 mice were lethally irradiated and reconstituted with allogeneic spleen cells in the absence or presence of ICOSL-blocking mAb. Mice reconstituted with allogeneic spleen cells experienced severe GVHD and died untreated within 6 9 days after transplantation. Mice treated with an anti-ICOSL mAb starting from day 3 after transplantation gained weight again and survived for at least additional 12 days, although the treatment was already stopped at day 11 after transplantation. In contrast, the anti-ICOSL treatment starting from day 0 did not prevent GVHD. The diff erence between therapeutic (day 3) and prophylactic (day 0) anti-ICOSL treatment was independent of CD25 + CD4 + regulatory T cells since their depletion did not abrogate the therapeutic eff ect of ICOSL blockade. Microarray analysis revealed IFN- and chemokine up-regulation in spleen cells of prophylactically treated mice, emphasizing kinetic dependence of acute GVHD modulation via blockade of ICOS:ICOSL interaction.
Only therapeutic ICOS:ICOSL blockade alleviates acute graft versus host disease.
Sex, Specimen part
View SamplesPolycystic ovarian syndrome (PCOS) is an endocrine disorder of the reproductive and metabolic axis in women during the reproductive age. In this study, we used a rat model exhibiting reproductive and metabolic abnormalities similar to human PCOS to unravel the molecular mechanisms underlining this complex syndrome.
Polycystic ovarian syndrome is accompanied by repression of gene signatures associated with biosynthesis and metabolism of steroids, cholesterol and lipids.
Specimen part
View SamplesAberrant placental gene expression associated with culture condition and/or deficiencies in transcriptome reprogramming are hypothesized to be the major cause of SCNT and IVP inefficiencies. Therefore, the main objective of this study was to invesitgate the dysregulated genes, molecular pathways and functional alteration in bovine placentas derived from SCNT and IVP pregnancies compared to their AI counterparts
Aberrant placenta gene expression pattern in bovine pregnancies established after transfer of cloned or in vitro produced embryos.
Specimen part, Treatment
View SamplesIn vivo microarray study of global gene expression changes in peripheral blood mononuclear cells (PBMCs) of Pietrain pigs during the stage of inatte immune and adaptive immune response to porcine reproductive and respiratory syndrome virus vaccination.
PBMC transcriptome profiles identifies potential candidate genes and functional networks controlling the innate and the adaptive immune response to PRRSV vaccine in Pietrain pig.
Sex
View SamplesGEP on Affymetrix U133+2.0 microarrays was performed on ex vivo cell-sorted Tfh from FL or TONS
CD10 delineates a subset of human IL-4 producing follicular helper T cells involved in the survival of follicular lymphoma B cells.
Specimen part, Treatment
View Samples