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Interpretation 29
Tier 2
PIM1
Variants
Primary Sites
Blood
Bone Marrow
Tumor Types
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Interpretation

PIM1 is a member of the PIM family of proteins which are proto-oncogenes, serine-threonine kinases with increased expression in a variety of malignancies. PIM1 expression appears to be up-regulated by STAT5, and has been found to be over-expressed in primary AML blast samples. In particular, PIM1 has associated with FLT3 mediated leukemogenesis in FLT3-ITD AML. PIM1 expression was noted to be 25-fold higher than in FLT3-ITD samples, as compared to wild type FLT3 (WT) AML samples. The PIM kinases, therefore, represent potential therapeutic targets in AML, particularly in those cases harboring FLT3-ITD mutations. According to one study, the small molecule inhibitor of PIM1, AR00459339, alone and in combination with a FLT3 inhibitor (AR00454200), resulted in significant cytotoxicity in FLT3-ITD cell lines and patient samples that strikingly parallels the effects of FLT3 inhibition. A variety of mutations have been reported throughout PIM1 in various types of malignancy including hematopoietic tumors, but PIM1 mutations appear to be extremely rare in acute myeloid leukemia and myelodysplasia.

Citations
  1. Fathi AT, et al. A potential therapeutic target for FLT3-ITD AML: PIM1 kinase. Leuk Res 2012;36(2):224-31
  2. Chen LS, et al. Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia. Blood 2011;118(3):693-702
Last updated: 2016-06-04 22:29:01 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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