Matches in SemOpenAlex for { <https://semopenalex.org/work/W2553533021> ?p ?o ?g. }
Showing items 1 to 78 of
78
with 100 items per page.
- W2553533021 abstract "Abstract Acute myeloid leukemia (AML) is a hematological malignancy resulting from the transformation of normal hematopoietic stem cell (HSC). Except for the intrinsic factors, it is acceptable that some extrinsic events from microenvironment could be the important co-factors in the development of leukemia. In addition to the specific component, as an extrinsic factor, interaction between HSC and bone marrow niche regulates HSCs fate. Disruption on the interactions also influences hematopoiesis. It has become evident that Rac members of Rho GTPases family are important molecules regulating HSCs interactions with hematopoietic microenvironment and activation of Rac1 are observed in a serials of leukemia cells. We previously reported that Rac1 is highly expressed in leukemia cells and found that activation of Rac1 GTPase lead to an increase in leukemia cells migration, chemotherapy resistance, quiescence and trafficking to bone marrow niche. Furthermore, we showed that Rac1 mediated the localization in niche is further attributable to the maintenance of LSC quiescence. In this study, we investigated the effects of active Rac1 GTPase in the transformation of HSC and determined if the activation of Rac1GTPase could promote the interaction of HSC with osteoblastic niche and further contribute to the leukomogenesis. By forced expression of a constitutively active form of Rac1 GTPase (Rac1 V12）in c-Kit+ hematopoietic stem/progenitor cell, we show that activation of Rac1 GTPase promotes cell migration, adhesion and colony formation, and also lead to an increase in the frequency of cells in quiescent state. Gene expression analysis shows that activation of Rac1 up-regulates the expression of several molecules that mediated the interaction of LSC with osteoblastic niche, as well as the cell cycle inhibitors such as p21, p27, and p57. Furthermore, we established a mouse model of acute myeloid leukemia by transduction murine c-kit+HSPC with Rac1 V12 combined with AML1-ETO9a, followed by transplantation into lethally irradiated mice. To investigate the role of Rac1 activation in leukemogenesis in vivo, we treated the AML1-ETO-Rac1 leukemia cells with Rac1 GTPase inhibitor EHT1846 and then transplanted into recipient mice. After 40 μM EHT1846 treatment, no engraftment of AML cells in recipient mice was observed. Kaplan-Meier analyses indicate that treatment with EHT1846 significantly prolongs survival of the transplanted mice. 20μM dose of EHT1846 was less effective. These data indicated that active Rac1 might be an important contributing factor to leukemogenesis. In addition, short-term homing assays showed that EHT 1846 treatment causes a marked inhibition of AML cell homing into both bone marrow and spleen as compared with controls, indicating that Rac1 mediated homing could be an important step and participated in the leukemogensis. Altogether, our data suggest that activation of Rac1 GTPase is critical for the interaction between HSCs with BM niche and even be contributed to leukemia development. Disclosures Wang: Novartis: Consultancy; Bristol Myers Squibb: Consultancy." @default.
- W2553533021 created "2016-11-30" @default.
- W2553533021 creator A5001014826 @default.
- W2553533021 creator A5003648502 @default.
- W2553533021 creator A5015102287 @default.
- W2553533021 creator A5064521563 @default.
- W2553533021 creator A5080605140 @default.
- W2553533021 creator A5086214965 @default.
- W2553533021 creator A5091284530 @default.
- W2553533021 date "2014-12-06" @default.
- W2553533021 modified "2023-09-26" @default.
- W2553533021 title "Rac1 Gtpase Promotes Hematopoietic Stem Cell Migration, Self-Renewal and Participates in Leukemia Initiation and Maintenance" @default.
- W2553533021 doi "https://doi.org/10.1182/blood.v124.21.2923.2923" @default.
- W2553533021 hasPublicationYear "2014" @default.
- W2553533021 type Work @default.
- W2553533021 sameAs 2553533021 @default.
- W2553533021 citedByCount "0" @default.
- W2553533021 crossrefType "journal-article" @default.
- W2553533021 hasAuthorship W2553533021A5001014826 @default.
- W2553533021 hasAuthorship W2553533021A5003648502 @default.
- W2553533021 hasAuthorship W2553533021A5015102287 @default.
- W2553533021 hasAuthorship W2553533021A5064521563 @default.
- W2553533021 hasAuthorship W2553533021A5080605140 @default.
- W2553533021 hasAuthorship W2553533021A5086214965 @default.
- W2553533021 hasAuthorship W2553533021A5091284530 @default.
- W2553533021 hasConcept C109159458 @default.
- W2553533021 hasConcept C201750760 @default.
- W2553533021 hasConcept C203014093 @default.
- W2553533021 hasConcept C207332259 @default.
- W2553533021 hasConcept C2778086970 @default.
- W2553533021 hasConcept C2778461978 @default.
- W2553533021 hasConcept C2779717556 @default.
- W2553533021 hasConcept C2780007613 @default.
- W2553533021 hasConcept C28328180 @default.
- W2553533021 hasConcept C502942594 @default.
- W2553533021 hasConcept C62478195 @default.
- W2553533021 hasConcept C86803240 @default.
- W2553533021 hasConcept C95444343 @default.
- W2553533021 hasConceptScore W2553533021C109159458 @default.
- W2553533021 hasConceptScore W2553533021C201750760 @default.
- W2553533021 hasConceptScore W2553533021C203014093 @default.
- W2553533021 hasConceptScore W2553533021C207332259 @default.
- W2553533021 hasConceptScore W2553533021C2778086970 @default.
- W2553533021 hasConceptScore W2553533021C2778461978 @default.
- W2553533021 hasConceptScore W2553533021C2779717556 @default.
- W2553533021 hasConceptScore W2553533021C2780007613 @default.
- W2553533021 hasConceptScore W2553533021C28328180 @default.
- W2553533021 hasConceptScore W2553533021C502942594 @default.
- W2553533021 hasConceptScore W2553533021C62478195 @default.
- W2553533021 hasConceptScore W2553533021C86803240 @default.
- W2553533021 hasConceptScore W2553533021C95444343 @default.
- W2553533021 hasLocation W25535330211 @default.
- W2553533021 hasOpenAccess W2553533021 @default.
- W2553533021 hasPrimaryLocation W25535330211 @default.
- W2553533021 hasRelatedWork W1951448021 @default.
- W2553533021 hasRelatedWork W1964653803 @default.
- W2553533021 hasRelatedWork W1976258760 @default.
- W2553533021 hasRelatedWork W1984156061 @default.
- W2553533021 hasRelatedWork W2041153640 @default.
- W2553533021 hasRelatedWork W2064771788 @default.
- W2553533021 hasRelatedWork W2086467407 @default.
- W2553533021 hasRelatedWork W2102434735 @default.
- W2553533021 hasRelatedWork W2289820450 @default.
- W2553533021 hasRelatedWork W2514464612 @default.
- W2553533021 hasRelatedWork W2528438222 @default.
- W2553533021 hasRelatedWork W2539876368 @default.
- W2553533021 hasRelatedWork W2558967213 @default.
- W2553533021 hasRelatedWork W2562269467 @default.
- W2553533021 hasRelatedWork W2565253062 @default.
- W2553533021 hasRelatedWork W2579953480 @default.
- W2553533021 hasRelatedWork W2604957298 @default.
- W2553533021 hasRelatedWork W2979523203 @default.
- W2553533021 hasRelatedWork W2979851102 @default.
- W2553533021 hasRelatedWork W2980973535 @default.
- W2553533021 isParatext "false" @default.
- W2553533021 isRetracted "false" @default.
- W2553533021 magId "2553533021" @default.
- W2553533021 workType "article" @default.