EphA2 Is a Therapy Target in EphA2-Positive Leukemias but Is Not Essential for Normal Hematopoiesis or Leukemia.

Charmsaz, Sara, Beckett, Kirrilee, Smith, Fiona M., Bruedigam, Claudia, Moore, Andrew S., Al-Ejeh, Fares, Lane, Steven W. and Boyd, Andrew W. (2015) EphA2 Is a Therapy Target in EphA2-Positive Leukemias but Is Not Essential for Normal Hematopoiesis or Leukemia.. PLoS One, 10 6: e0130692-e0130692. doi:10.1371/journal.pone.0130692

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Author Charmsaz, Sara
Beckett, Kirrilee
Smith, Fiona M.
Bruedigam, Claudia
Moore, Andrew S.
Al-Ejeh, Fares
Lane, Steven W.
Boyd, Andrew W.
Title EphA2 Is a Therapy Target in EphA2-Positive Leukemias but Is Not Essential for Normal Hematopoiesis or Leukemia.
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2015-06-17
Sub-type Article (original research)
DOI 10.1371/journal.pone.0130692
Open Access Status DOI
Volume 10
Issue 6
Start page e0130692
End page e0130692
Total pages 17
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2016
Language eng
Formatted abstract
Members of the Eph family of receptor tyrosine kinases and their membrane bound ephrin ligands have been shown to play critical roles in many developmental processes and more recently have been implicated in both normal and pathological processes in post-embryonic tissues. In particular, expression studies of Eph receptors and limited functional studies have demonstrated a role for the Eph/ephrin system in hematopoiesis and leukemogenesis. In particular, EphA2 was reported on hematopoietic stem cells and stromal cells. There are also reports of EphA2 expression in many different types of malignancies including leukemia, however there is a lack of knowledge in understanding the role of EphA2 in hematopoiesis and leukemogenesis. We explored the role of EphA2 in hematopoiesis by analyzing wild type and EphA2 knockout mice. Mature, differentiated cells, progenitors and hematopoietic stem cells derived from knockout and control mice were analyzed and no significant abnormality was detected. These studies showed that EphA2 does not have an obligatory role in normal hematopoiesis. Comparative studies using EphA2-negative MLL-AF9 leukemias derived from EphA2-knockout animals showed that there was no detectable functional role for EphA2 in the initiation or progression of the leukemic process. However, expression of EphA2 in leukemias initiated by MLL-AF9 suggested that this protein might be a possible therapy target in this type of leukemia. We showed that treatment with EphA2 monoclonal antibody IF7 alone had no effect on tumorigenicity and latency of the MLL-AF9 leukemias, while targeting of EphA2 using EphA2 monoclonal antibody with a radioactive payload significantly impaired the leukemic process. Altogether, these results identify EphA2 as a potential radio-therapeutic target in leukemias with MLL translocation.
Keyword Leukaemia
EphA2
Haematopoiesis
MLL
KMT2A
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
 
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Created: Wed, 24 Jun 2015, 09:24:12 EST by Andrew Moore on behalf of UQ Diamantina Institute