Background and Objective:

There are 3 members in Pim family, Pim-1, Pim-2 and Pim-3. They are serine/threonine kinase coding proto-oncogene. It is reported that Pim-1 plays a role in solid tumor, leukemia and polycythemia vera, et al. Pim-3, as a newly cloned oncogene has discovered to functioning in hepatic carcinoma, pancreatic cancer, et al. We are trying to find out the roles of Pim1 in acute myeloid leukemia.

Methods:

1 Evaluate the expressions of Pim family genes in acute myeloid leukemia patients and analysis the profile of Pim expressions with clinical characteristics.

2 Up-regulating the expression of Pim1 in AML cell lines by transient transfection or long-term infection through GFP-expressing plasmids and lenti-virus system and analyze the proliferation, apoptosis and chemotaxis features of the transfected AML cell lines.

Results:

1 Our investigation showed that Pim-1 is up-regulated in around 15% of acute myeloid leukemia (AML) patients.

2 As shown in growth curves and apoptosis assays, over expression of Pim-1induces growth up-regulation and anti-apoptosis. We hypothesized that phenomenon could be originated from the enhanced expression of c-myc, cyclin D1 and Bad phosphorylation shown in western blotting analysis.

3 Our chemotaxis assay and bone marrow stromal cell co-culture model demonstrated that overexpression of Pim-1can enhance the AML cells chemotactic movement toward SDF-1¦Á, with calcium influx increment and phosphorylation of CXCR4.

4 Flow cytometry analysis and confocal immunofluorescence observation demonstrated the up-regulated CXCR4 expression and internalization induced by SDF-1¦Á.

5 We also checked the angiogenesis and adhesion molecule during the process but did not show any contribution.

Conclusion:

Pim-1, beyond as an oncogene, can promote growth or anti-apoptosis of AML cells, can interact with microenviroment through SDF-1¦Á-CXCR4 axis. The interplay between AML cells and microenviroment mediated by Pim-1 can make sense in AML target therapy and make a good adjunctive for transplantation conditioning regimen.

Figure 1.
Figure 1. Expression of Pim1 in AML patients and control
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Expression of Pim1 in AML patients and control

Figure 1.
Figure 1. Expression of Pim1 in AML patients and control
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Expression of Pim1 in AML patients and control

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Disclosures

No relevant conflicts of interest to declare.

Topics:
leukemia, myelocytic, acute, oncogenes, proto-oncogene proteins c-pim-1, cxcr4 receptors, calcium, carcinoma, hepatocellular, cell adhesion molecules, coculture techniques, cyclin d1, flow cytometry

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2015 by The American Society of Hematology
2015
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