Abstract 3297

In this study we observe that Livin plays a role in thrombopoiesis. Livin is a member of the Inhibitor of Apoptosis Proteins (IAP) family of intracellular anti-apoptotic proteins that acts by binding and inhibiting caspases. Previously we found that Livin is unique among the IAP members as upon strong apoptotic stimuli, it is specifically cleaved by caspases to produce a truncated protein (tLivin) that has a paradoxical pro-apoptotic activity. Here we have shown that Livin is expressed in normal mature bone marrow MK and in platelets.

Objective:

The objective of this study was to evaluate the potential role of Livin in thrombopoiesis.

Methods:

We studied Livin expression in normal BM using immunohistochemistry staining. We studied the ability of primary MK generated from CD34+progenitor cells over-expressing Livin to produce platelets. While, the human cell line, LAMA-84, was induced by a phorbol myristic acid (PMA) to differentiate to megakaryocytes (MK) to evaluate the potential role of Livin in thrombopoiesis.

Results and conclusions:

Livin over-expression in CD34+ progenitor cells induced differentiation of these cells into MK and increased the ability of these primary MK to produce platelets. LAMA-84, upon differentiation into MK, produces platelets that are functional and capable of aggregating. This thrombopoiesis was accompanied by increased Livin expression and downregulation of other IAPs: XIAP and Survivin. Our results show that Livin plays a dual role in thrombopoiesis, demonstrating both an anti and pro-apoptotic role in cell activity.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
caspases, cd34 antigens, inhibitor-of-apoptosis protein, megakaryocytes, myristic acid, phorbols, platelet production, survivin, immunohistochemistry, blood platelets

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2012 by The American Society of Hematology
2012
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