Contributions
Abstract: PB1659
Type: Publication Only
Background
Acute myeloid leukemia (AML) is the a haematological malignancy characterised by the over proliferation and block in differentiation of clonal stem cells. In leukaemia potential biomarkers such as S100A8 could assesses the progression and remission of AML.
Aims
S100A8 and S100A9 (Ca2+ binding helix E-loop-helix-F hand), are inflammatory markers which are also suggested to promote chemoresistance by stimulation of autophagy. Microarray data from the Chevassut lab shows that both S100A8 and S100A9 transcripts are downregulated by the BET-bromodomain inhibitor JQ1 in AML cell lines. We aimed to investigate this response in AML patient bone marrow samples and cell lines.
Methods
We used AML cell line including OCI-AML2, OCI-AML3 and THP-1 in addition to AML patient bone marrow samples and healthy volunteer samples. We carried out RT-qPCR and immunocytochemistry and western blotting techniques to look at levels of S100A8 and S100A9 in samples.
Results
Here we show that levels of S100A8 and S100A9 mRNA levels are suppressed in response to JQ1 in the AML cells lines OCI-AML2, OCI-AML3 and THP-1. We find also that protein levels of S100A8 and S100A9 are downregulated in response to JQ1 in OCI-AML3. In bone marrow samples of 17 AML patients with different cytogenetic profiles, the relative expression of S100A8 and S100A9 was found to be variable amongst the samples but also in comparison to OCI-AML3 cell line. In further experiments using AML patient bone marrow samples, treatment with JQ1 showed suppression of S100A8 and S100A9 in some patient samples but enhanced expression in other bone marrows. In peripheral blood samples of healthy volunteers, we found that treatment with JQ1 showed notable suppression of both S100A8 and S100A9; with a greater suppression being observed in the monocyte fraction of the samples.
Conclusion
Our data suggests that JQ1 regulates the expression of S100A8 and S100A9 in AML. The variability of the response seen amongst AML patient samples and AML cell lines may be reflective of the genetic profiles driving the leukaemogenic process in these samples Further work may give more detailed insight into the mechanisms of action and potential use of S100A8 and S100A9 in AML prognostic markers.
Session topic: 3. Acute myeloid leukemia - Biology
Keyword(s): Prognostic factor, Leukemia cell line, Calcium, Acute Myeloid Leukemia
Abstract: PB1659
Type: Publication Only
Background
Acute myeloid leukemia (AML) is the a haematological malignancy characterised by the over proliferation and block in differentiation of clonal stem cells. In leukaemia potential biomarkers such as S100A8 could assesses the progression and remission of AML.
Aims
S100A8 and S100A9 (Ca2+ binding helix E-loop-helix-F hand), are inflammatory markers which are also suggested to promote chemoresistance by stimulation of autophagy. Microarray data from the Chevassut lab shows that both S100A8 and S100A9 transcripts are downregulated by the BET-bromodomain inhibitor JQ1 in AML cell lines. We aimed to investigate this response in AML patient bone marrow samples and cell lines.
Methods
We used AML cell line including OCI-AML2, OCI-AML3 and THP-1 in addition to AML patient bone marrow samples and healthy volunteer samples. We carried out RT-qPCR and immunocytochemistry and western blotting techniques to look at levels of S100A8 and S100A9 in samples.
Results
Here we show that levels of S100A8 and S100A9 mRNA levels are suppressed in response to JQ1 in the AML cells lines OCI-AML2, OCI-AML3 and THP-1. We find also that protein levels of S100A8 and S100A9 are downregulated in response to JQ1 in OCI-AML3. In bone marrow samples of 17 AML patients with different cytogenetic profiles, the relative expression of S100A8 and S100A9 was found to be variable amongst the samples but also in comparison to OCI-AML3 cell line. In further experiments using AML patient bone marrow samples, treatment with JQ1 showed suppression of S100A8 and S100A9 in some patient samples but enhanced expression in other bone marrows. In peripheral blood samples of healthy volunteers, we found that treatment with JQ1 showed notable suppression of both S100A8 and S100A9; with a greater suppression being observed in the monocyte fraction of the samples.
Conclusion
Our data suggests that JQ1 regulates the expression of S100A8 and S100A9 in AML. The variability of the response seen amongst AML patient samples and AML cell lines may be reflective of the genetic profiles driving the leukaemogenic process in these samples Further work may give more detailed insight into the mechanisms of action and potential use of S100A8 and S100A9 in AML prognostic markers.
Session topic: 3. Acute myeloid leukemia - Biology
Keyword(s): Prognostic factor, Leukemia cell line, Calcium, Acute Myeloid Leukemia