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Druid, Pia
Publications (3 of 3) Show all publications
Nordigården, A., Halvarsson, C., Tang, Y.-j., Druid, P. & Jönsson, J.-I. (2012). A COMPARATIVE STUDY OF VARIOUS FLT3-ITD MUTATIONS ISOLATED FROM ACUTE MYELOID LEUKEMIA PATIENTS in EXPERIMENTAL HEMATOLOGY, vol 40, issue 8, pp S130-S131. In: EXPERIMENTAL HEMATOLOGY (pp. S130-S131). Elsevier, 40(8)
Open this publication in new window or tab >>A COMPARATIVE STUDY OF VARIOUS FLT3-ITD MUTATIONS ISOLATED FROM ACUTE MYELOID LEUKEMIA PATIENTS in EXPERIMENTAL HEMATOLOGY, vol 40, issue 8, pp S130-S131
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2012 (English)In: EXPERIMENTAL HEMATOLOGY, Elsevier , 2012, Vol. 40, no 8, p. S130-S131Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Elsevier, 2012
Series
EXPERIMENTAL HEMATOLOGY, ISSN 0301-472X
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-80785 (URN)000307319600202 ()
Available from: 2012-08-30 Created: 2012-08-30 Last updated: 2012-08-30
Nordigården, A., Zetterblad, J., Trinks, C., Green, H., Eliasson, P., Druid, P., . . . Jönsson, J.-I. (2011). Irreversible pan-ERBB inhibitor canertinib elicits anti-leukaemic effects and induces the regression of FLT3-ITD transformed cells in mice. British Journal of Haematology, 155(2), 198-208
Open this publication in new window or tab >>Irreversible pan-ERBB inhibitor canertinib elicits anti-leukaemic effects and induces the regression of FLT3-ITD transformed cells in mice
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2011 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 155, no 2, p. 198-208Article in journal (Refereed) Published
Abstract [en]

Recent findings have indicated that tyrosine kinase inhibitors (TKIs) targeting the ERBB receptor family display anti-leukaemic effects, despite the lack of receptor expression on human leukaemic cells. The occurrence of activating mutations in the gene encoding FMS-like tyrosine kinase 3 (FLT3) in patients with acute myeloid leukaemia (AML) has rendered inhibition of this receptor a promising therapeutic target. Due to possibility of cross-reactivity, we investigated the effect of the irreversible pan-ERBB inhibitor canertinib (CI-1033) on leukaemic cells expressing FLT3. The drug had anti-proliferative and apoptotic effects on primary AML cells and human leukaemic cell lines expressing mutated FLT3. In several AML patient samples, a blast cell population expressing FLT3-internal tandem duplication (ITD) was eradicated by canertinib. Canertinib inhibited receptor autophosphorylation and kinase activity of both mutated and FLT3 ligand stimulated wildtype FLT3, leading to inhibition of the PI3-kinase and MAP kinase pathways. Apoptotic induction was dependent on pro-apoptotic BH3-only protein BCL2L11/BIM because siRNA silencing attenuated apoptosis. Moreover, the drug induced regression of cells expressing FLT3-ITD in a murine in vivo-transplantation model at previously described tolerated doses. These results indicate that canertinib, as an irreversible TKI, could constitute a novel treatment regimen in patients with mutated or overexpressed FLT3.

Place, publisher, year, edition, pages
Blackwell Publishing, 2011
Keywords
acute myeloid leukaemia, apoptosis, signalling, drugs, murine model, leukaemia therapy
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-72031 (URN)10.1111/j.1365-2141.2011.08819.x (DOI)000296063400006 ()
Note
Funding Agencies|Swedish Cancer Foundation||Swedish Childrens Cancer Foundation||Swedish Research Council||County Council of Ostergotland||Cancer Foundation of Ostergotland||Ollie and Elof Ericssons Foundation||Available from: 2011-11-11 Created: 2011-11-11 Last updated: 2017-12-08
Forsberg, M., Druid, P., Zheng, L., Stendahl, O. & Särndahl, E. (2003). Activation of Rac2 and Cdc42 on Fc and complement receptor ligation in human neutrophils. Journal of Leukocyte Biology, 74(4), 611-619
Open this publication in new window or tab >>Activation of Rac2 and Cdc42 on Fc and complement receptor ligation in human neutrophils
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2003 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 74, no 4, p. 611-619Article in journal (Refereed) Published
Abstract [en]

Phagocytosis is a complex process engaging a concerted action of signal-transduction cascades that leads to ingestion, subsequent phagolysosome fusion, and oxidative activation. We have previously shown that in human neutrophils, C3bi-mediated phagocytosis elicits a significant oxidative response, suggesting that activation of the small GTPase Rac is involved in this process. This is contradictory to macrophages, where only Fc receptor for immunoglobulin G (FcγR)-mediated activation is Rac-dependent. The present study shows that engagement of the complement receptor 3 (CR3) and FcγR and CR3- and FcγR-mediated phagocytosis activates Rac, as well as Cdc42. Furthermore, following receptor-engagement of the CR3 or FcγRs, a downstream target of these small GTPases, p21-activated kinase, becomes phosphorylated, and Rac2 is translocated to the membrane fraction. Using the methyltransferase inhibitors N-acetyl-S-farnesyl-L-cysteine and N-acetyl-S-geranylgeranyl-L-cysteine, we found that the phagocytic uptake of bacteria was not Rac2- or Cdc42-dependent, whereas the oxidative activation was decreased. In conclusion, our results indicate that in neutrophils, Rac2 and Cdc42 are involved in FcR- and CR3-induced activation and for properly functioning signal transduction involved in the generation of oxygen radicals.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24991 (URN)10.1189/jlb.1102525 (DOI)9411 (Local ID)9411 (Archive number)9411 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
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