Hematopoiesis and microenvironment in hematological malignancies

Cheng, Hui; Sun, Guoxiang; Cheng, Tao

doi:10.1016/j.cr.2018.08.002

Cited by 20 publications

(17 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to cellular communication, exosomes are known to be associated with immune reactions, cancer viability and invasion, antigen presentation, and cell migration and differentiation (53). Recently, a number of studies have demonstrated the role of these EVs in hematological malignancies (21)(22)(23), as well as their involvement at different diseases phases (33,53).…”

Section: Discussionmentioning

confidence: 99%

“…currently, at least to the best of our knowledge, there are no studies available reporting the possibility of enriching the tumor-derived exosome fraction in patients affected by different types of leukemia. However, certain groups have revealed that exosomes isolated from cell line cultures modulate the crosstalk between leukemia cells and the bone marrow (BM) microenvironment, and that they also carry molecular tumor markers (21)(22)(23)(24). Moreover, recent studies have indicated that leukemia-derived exosomes can be utilized as prognostic (25), diagnostic (26) and therapeutic biomarkers (27) for individuals suffering from different hematologic malignancies, such as acute myeloid leukemia (28)(29)(30), multiple myeloma (31) and chronic lymphocytic leukemia (32).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia

et al. 2019

View full text Add to dashboard Cite

due to the discovery of their role in intra-cellular communications, exosomes, which carry information specific to the cell of origin, have garnered considerable attention in cancer research. Moreover, there is evidence to suggest the possibility of isolating different exosome sub-populations based on target antigens at the cell surface. Philadelphia chromosome-positive (Ph +) chronic myeloid leukemia (cML) is a clonal myeloproliferative neoplasia characterized by the breakpoint cluster region-proto-oncogene 1 tyrosine-protein kinase (BcR-ABL1) fusion-gene, derived from the t (9;22) translocation. Tyrosine kinase inhibitors (TKIs) target BcR-ABL1 protein and induce major or deep molecular responses in the majority of patients. despite the fact that several studies have demonstrated the persistence of leukemic cells in the bone marrow niche, even following treatment, TKIs prolong patient survival time and facilitate treatment-free remission. These characteristics render cML a plausible model for investigating the feasibility of tumor-derived exosome fraction enrichment. In the present study, patients in the chronic phase (cP) of CML were treated with TKIs, and the quantification of the BCR-ABL1 exosomal transcript was performed using digital PcR (dPcR). The possibility of tumor-derived exosomes enrichment was confirmed, and for the first time, to the best of our knowledge, the detection of the BcR-ABL1 transcript highlighted the presence of active leukemic cells in patients with CP-CML. According to these findings, tumor-derived exosomes may be considered a novel tool for the identification of active leukemic cells, and for the assessment of innovative monitoring focused on the biological functions of exosomes in cML.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Hematopoiesis is a precisely modulated multi-step process including hematopoietic stem cell (HSC) selfrenewal and hematopoietic stem/progenitor cell differentiation [1,2]. Erythropoiesis and megakaryopoiesis are important parts of hematopoiesis [3,4]. Normal erythropoiesis produces about 10 11 new red blood cells (RBCs) every day in an adult human through the commitment of hematopoietic stem cells into erythroid progenitors, which subsequently differentiate into mature RBCs [5,6].…”

Section: Introductionmentioning

confidence: 99%

CRKL but not CRKII Inhibits Erythropoiesis and Megakaryopoiesis of CML via Inactivating Raf/MEK/ERK/Elk-1 Pathway

Guo

Zhang

Yan

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: As members of the CT10 regulation of kinase (CRK) adaptor protein family, CRK-like (CRKL) and CRKII are involved in cell proliferation, survival, adhesion, migration and differentiation. However, the exact role and underlying mechanism of CRKL and CRKII in leukemic cell differentiation are still unknown. Methods: Quantitative real-time qPCR (qRT-PCR) was used to detect the expression levels of CRKL and CRKII in chronic myeloid leukemia (CML) patients and complete remission (CR) patients; Western blotting (WB) was used to measure the expression levels of CRKL and CRKII during hemin-induced erythroid differentiation of K562 cells; Benzidine staining, isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis, cDNA microarray assay, qRT-PCR and WB were used to examine the effects of CRKL and CRKII deregulation on erythroid and megakaryocyte differentiation of K562 cells; PD98059 was used to investigate the underlying mechanism of CRKL in erythropoiesis and megakaryopoiesis. Results: CRKL was found to be overexpressed in chronic myeloid leukemia (CML) patients compared with normal samples, while its expression level was lower in CR patients than in corresponding CML patients. The CRKL expression level was significantly decreased during the erythroid differentiation of K562 cells following hemin treatment. Moreover, CRKL downregulation promoted erythroid and megakaryocyte differentiation of K562 cells accompanied by increased expression level of the erythroid differentiation markers γ-globin, glycophorin (GPA) and the megakaryocyte differentiation markers CD41, CD61. Furthermore, gene microarray and iTRAQ quantitative proteomic analysis showed that CRKL downregulation increased hemoglobin (HB) molecules HBD, HBA1, HBA2, HBZ, HBE1, HBG1 and globin transcription factor 1 (GATA1), high-mobility group protein (HMGB2) expression levels. Mechanistically, CRKL inhibited erythroid and megakaryocyte differentiation of K562 cell via inactivating Raf/MEK/ERK/Elk-1 pathway. Conversely, CRKII was only slightly overexpressed in CML patients and had no effect on erythroid differentiation of K562 cells. Conclusions: Taken together, our results demonstrate that CRKL but not CRKII contributes to development, progression, erythropoiesis and megakaryopoiesis of CML, providing novel insights into effective diagnosis and therapy for CML patients.

show abstract

“…Different cytokines achieves this transformati on through variety pathways and thereby mediates LSC mobilization, homing and drug resistance, which eventually become an important cause of clinical recurrence (9). Treatment to hijacked or transformed niches may provide no vel therapies to delay the leukemia relapse (10).…”

Section: Introductionmentioning

confidence: 99%

Bioinformatics-based Prediction of the mechanism and targets for BushenjieduDecoction in preventing relapse of acute leukemia

Sun

Feng-ying

Wei

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Leukemia is a lethal myeloproliferative disorder, its’ relapse following chemotherapy is the major concern in clinical practice. For a long time, we found that traditional Chinese medicines such as Bushenjiedudecoction (BSJD) have significant effects on delaying relapse. However, the underlying mechanisms are not clear, which limits the clinical application of BSJD decoction. Methods: Therefore, we tried to make some explorations in this study. We isolated mesenchymal stem cells (MSC) after treated them with BSJD for proteomic analysis. And then 109 targets were screened out through analysis of the shared proteins of that affected by BSJD and those related to leukemia. Subsequently, the data were analyzed by GO functions, KEGG pathways, PPI network and topological analysis, and then some nodes were selected for animal experiment. Results: As a result, we demonstrated the effective targets of BSJD on MSC through bioinformatics analysis and explored the potential mechanism of BSJD from its influence on niches.These targets contains Hspb1、Dnmt1、Mmp2、Thbs1、Crebbp、Hmgb1、Acta2、Cdkn1b、Atg7、Tsc2 and Icam1. Afterwards, we confirmed BSJD reduced the gene expression of ICAM-1 through cultured MSC in vitro.Conclusions: We screened the potential targets of BSJD on MSC through proteomics and bioinformatics analysis, and selected some genes for experimental verification. These studies demonstrated the effect of BSJD on MSC. We hope that this research method could provide a new way of systematically studying the effects of traditional Chinese medicine on diseases.

show abstract

Hematopoiesis and microenvironment in hematological malignancies

Cited by 20 publications

References 55 publications

Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia

Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia

CRKL but not CRKII Inhibits Erythropoiesis and Megakaryopoiesis of CML via Inactivating Raf/MEK/ERK/Elk-1 Pathway

Bioinformatics-based Prediction of the mechanism and targets for BushenjieduDecoction in preventing relapse of acute leukemia

Contact Info

Product

Resources

About