Global gene expression analysis of CD10+/CD19+ pre B lymphoblasts from bone marrow and peripheral blood of B-ALL patients
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PROVIDER: PRJNA708336 | ENA |
REPOSITORIES: ENA
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Project description:Acute lymphoblastic leukemia (ALL) is the most frequent childhood cancer. Mexico City has one of the highest incidences in the world, with pediatric patients showing a poor response to conventional therapy, low survival rates and high relapse rates. We performed a global gene expression profile of pre B lymphoblasts from bone marrow (BM) and peripheral blood (PB) samples from B-ALL patients to find the upregulated and downregulated genes in both cell populations in the context of this childhood cancer.
2022-04-27 | GSE168593 | GEO
Project description:We used microarrays to analyze the gene expression profile of CD34+CD45RA+CD7+, CD34+CD45RA+CD10+CD19- and CD34+CD45+CD7-CD10-CD19- HPCs isolated from umbilical cord blood CD34+CD45RA+CD7+(CD10-) and CD34+CD45RA+CD10+(CD7-CD19-) HPCs correspond respectively to prothymocytes and early pre-proB precursors. CD34+CD45RA+CD7-CD10-CD19- HPCs correspond to lympho-granulo-macrophagic precursors
2011-05-25 | GSE29522 | GEO
Project description:We used microarrays to analyze the gene expression profile of CD34+CD45RA+CD7+, CD34+CD45RA+CD10+CD19- and CD34+CD45+CD7-CD10-CD19- HPCs isolated from umbilical cord blood CD34+CD45RA+CD7+(CD10-) and CD34+CD45RA+CD10+(CD7-CD19-) HPCs correspond respectively to prothymocytes and early pre-proB precursors. CD34+CD45RA+CD7-CD10-CD19- HPCs correspond to lympho-granulo-macrophagic precursors The corresponding populations were sorted from total CD34+ HPCs isolated from 2 or 3 individual donors
2011-05-25 | E-GEOD-29522 | biostudies-arrayexpress
Project description:The tunica adventitia ensheaths arteries and veins and contains presumptive mesenchymal stem cells (MSCs) involved in vascular remodeling. We show here that a subset of human adventitial cells expresses the CD10/CALLA cell surface metalloprotease. Sorted CD10+ adventitial cells developed promptly in culture into MSCs, exhibiting higher proliferation, clonogenic and osteogenic potentials than CD10- counterparts. CD10+ adventitial cells increased expression of the cell cycle protein CCND2 via ERK1/2 and prompted NELL1 expression via NF-κB. CD10 expression was upregulated in CD10+ adventitial cells through neural secreted protein sonic hedgehog-mediated Gli1 signaling. These results suggest that CD10 expression, which marks rapidly dividing cells in other normal and malignant cell lineages, plays a role in MSC homeostasis in human tissues.
2019-06-11 | GSE115557 | GEO
Project description:Comparison of human BCP-ALL MLL-r and normal CD19+CD10+ precursor B-cell transcriptomes
| PRJNA736019 | ENA
Project description:Studies of adult human hematopoiesis have until now relied on the expression of CD10 to define lymphoid commitment. We report a novel lymphoid-primed population in human bone marrow that is generated from hematopoietic stem cells (HSC) prior to the onset of CD10 expression and B cell commitment, and is identified by high levels of the homing molecule L-selectin (CD62L). CD10-CD62Lhi progenitors have full lymphoid (B/T/NK) potential, and show reduced myeloid and absent erythroid potential. Genome-wide gene expression analysis demonstrates that the CD10-CD62Lhi population represents an intermediate stage of differentiation between CD34+CD38- HSC and CD34+lin-CD10+ progenitors marked by down-regulation of TAL1 and MPL, upregulation of E2A, CD3E and IL2RG expression, and absent B cell commitment or RAG1/2 expression. Immature CD34+CD1a- thymocytes are also CD62Lhi and L-selectin ligands are expressed at the cortico-medullary junction, suggesting a possible role for L-selectin in human thymic homing. These studies identify the earliest stage of lymphoid priming in human bone marrow.
2012-08-15 | GSE35685 | GEO
Project description:Mexico City has one of the highest incidences of acute lymphoblastic leukemia (ALL) globally, with patients showing low survival, and high relapse rates. To gain more insight into the molecular features of B-ALL in Mexican children, we isolated CD10 + /CD19 + precursor B lymphoblasts from four bone marrow and nine peripheral blood samples of B-ALL patients using a fluorescence-activated cell sorting protocol. The global gene expression profile (BM vs PB) revealed 136 differentially expressed genes; 62 were upregulated (45.6%) and 74 were downregulated (54.4%). Pearson's correlation coefficient was calculated to determine the similarity between pre-B lymphoblast populations. We selected 26 highly significant genes and validated 21 by RT-qPCR (CNN3, STON2, CALN1, RUNX2, GADD45A, CDC45, CDC20, PLK1, AIDA, HCK, LY86, GPR65, PIK3CG, LILRB2, IL7R, TCL1A, DOCK1, HIST1H3G, PTPN14, CD72, and NT5E). The gene set enrichment analysis of the total expression matrix and the ingenuity pathway analysis of the 136 differentially expressed genes showed that the cell cycle was altered in the bone marrow with four overexpressed genes (PLK1, CDC20, CDC45, and GADD45A) and a low expression of IL7R and PIK3CG, which are involved in B cell differentiation. A comparative bioinformatics analysis of 15 bone marrow and 10 peripheral blood samples from Hispanic B-ALL patients collected by the TARGET program, corroborated the genes observed, except for PIK3CG. We conclude the Mexican and the Hispanic B-ALL patients studied present common driver alterations and histotype-specific mutations that could facilitate risk stratification and diagnostic accuracy and serve as potential therapeutic targets.
| S-EPMC9023642 | biostudies-literature
Project description:Studies of adult human hematopoiesis have until now relied on the expression of CD10 to define lymphoid commitment. We report a novel lymphoid-primed population in human bone marrow that is generated from hematopoietic stem cells (HSC) prior to the onset of CD10 expression and B cell commitment, and is identified by high levels of the homing molecule L-selectin (CD62L). CD10-CD62Lhi progenitors have full lymphoid (B/T/NK) potential, and show reduced myeloid and absent erythroid potential. Genome-wide gene expression analysis demonstrates that the CD10-CD62Lhi population represents an intermediate stage of differentiation between CD34+CD38- HSC and CD34+lin-CD10+ progenitors marked by down-regulation of TAL1 and MPL, upregulation of E2A, CD3E and IL2RG expression, and absent B cell commitment or RAG1/2 expression. Immature CD34+CD1a- thymocytes are also CD62Lhi and L-selectin ligands are expressed at the cortico-medullary junction, suggesting a possible role for L-selectin in human thymic homing. These studies identify the earliest stage of lymphoid priming in human bone marrow. Freshly harvested human bone marrow was ficoll purified, enriched for CD34+, and then FACS sorted. It was then sorted into 3 samples CD34+CD38-, CD34+ CD10- CD62L++, and CD34+ CD10+, with 3 independent biological replicates
2012-08-14 | E-GEOD-35685 | biostudies-arrayexpress
Project description:Chimeric antigen receptor T cell (CAR-T) targeting the CD19 antigen represents an innovative therapeutic approach to improve the outcome of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Yet, despite a high initial remission rate, CAR-T therapy ultimately fails for some patients. Notably, around half of relapsing patients develop CD19 negative (CD19neg) B-ALL allowing leukemic cells to evade CD19-targeted therapy. Herein, we investigate leukemic cells of a relapsing B-ALL patient, at two-time points: before (T1) and after (T2) anti-CD19 CAR-T treatment. We show that at T2, the B-ALL relapse is CD19 negative due to the expression of a non-functional CD19 transcript retaining intron 2. Then, using single-cell RNA sequencing (scRNAseq) approach, we demonstrate that CD19neg leukemic cells were present before CAR-T cell therapy and thus that the relapse results from the selection of these rare CD19neg B-ALL clones. In conclusion, our study shows that scRNAseq profiling can reveal pre-existing CD19neg subclones, raising the possibility to assess the risk of targeted therapy failure.
2020-12-11 | GSE153697 | GEO
Project description:Studies here respond to two long-standing questions: Are human "pre/pro-B" CD34(+)CD10(-)CD19(+) and "common lymphoid progenitor (CLP)/early-B" CD34(+)CD10(+)CD19(-) alternate precursors to "pro-B" CD34(+)CD19(+)CD10(+) cells, and do the pro-B cells that arise from these progenitors belong to the same or distinct B-cell development pathways? Using flow cytometry, gene expression profiling, and Ig V(H)-D-J(H) sequencing, we monitor the initial 10 generations of development of sorted cord blood CD34(high)Lineage(-) pluripotential progenitors growing in bone marrow S17 stroma cocultures. We show that (i) multipotent progenitors (CD34(+)CD45RA(+)CD10(-)CD19(-)) directly generate an initial wave of Pax5(+)TdT(-) "unilineage" pre/pro-B cells and a later wave of "multilineage" CLP/early-B cells and (ii) the cells generated in these successive stages act as precursors for distinct pro-B cells through two independent layered pathways. Studies by others have tracked the origin of B-lineage leukemias in elderly mice to the mouse B-1a pre/pro-B lineage, which lacks the TdT activity that diversifies the V(H)-D-J(H) Ig heavy chain joints found in the early-B or B-2 lineage. Here, we show a similar divergence in human B-cell development pathways between the Pax5(+)TdT(-) pre/pro-B differentiation pathway that gives rise to infant B-lineage leukemias and the early-B pathway.
| S-EPMC2851857 | biostudies-other