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| Status |
Public on Sep 19, 2012 |
| Title |
In vitro and in vivo monitoring of valproic acid effects on gene expression signatures in adult acute myeloid leukemia |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
PURPOSE: Inhibitors of histone deacetylases (HDACIs) like valproic acid (VPA) display activity in murine leukemia models, and induce tumor-selective cytoxicity against blasts from patients with acute myeloid leukemia (AML). However, despite of the existing knowledge of the potential function of HDACIs, there remain many unsolved questions especially regarding the factors that determine whether a cancer cell undergoes cell cycle arrest, differentiation, or death in response to HDACIs. Furthermore, there is still limited data on HDACIs effects in vivo, as well as HDACIs function in combination with standard induction chemotherapy, as most studies evaluated HDACIs as single agent in vitro. Thus, our first goal was to determine a VPA response signature in different myeloid leukemia cell lines in vitro, followed by an in vivo analysis of VPA effects in blasts from adult de novo AML patients entered within two randomized multicenter treatment trials of the German-Austrian AML Study Group.
PATIENTS AND METHODS: To define a VPA in vitro response signature we profiled gene expression in myeloid leukemia cell lines (HL60, NB4, HEL, and K-562) following 48 hours of VPA treatment by using DNA Microarray technology. Next, we evaluated the VPA effects on gene expression in AML samples collected within the AMLSG 07-04 trial for younger (age<60yrs) and within the AMLSG 06-04 trial for older adults (age>60yrs), in which patients are randomized to receive standard induction chemotherapy (idarubicine, cytarabine, and etoposide = ICE) with or without concomitant VPA. We profiled gene expression in diagnostic AML blasts and following 48 hours of treatment with ICE or ICE/VPA.
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| Overall design |
cDNA microarrays from the Stanford Functional Genomics Facility were used to perform mRNA transcript profiling of 4 leukemia cell lines treated with 1mM VPA for 48 hours in comparison to untreated cell lines, and to perform mRNA transcript profiling of freshly-frozen, from matched acute myeloid leukemia peripheral blood specimens collected from 14 AML patients at diagnosis and following 48 hours of treatment with either chemotherapy +/- VPA.
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| Contributor(s) |
Bullinger L |
| Citation(s) |
27309669, 29854289 |
| |
| Submission date |
Sep 20, 2011 |
| Last update date |
May 22, 2019 |
| Contact name |
Jonathan Pollack |
| E-mail(s) |
[email protected]
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| Phone |
650-736-1987
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| Organization name |
Stanford University
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| Department |
Pathology
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| Lab |
Pollack Lab
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| Street address |
269 Campus Drive, CCSR3245A
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| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305-5176 |
| Country |
USA |
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| Platforms (1) |
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| Samples (43)
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| GSM798923 |
Patient 1, 48 h, in vivo |
| GSM798924 |
HEL, 0 h against 48 h 1mM VPA |
| GSM798925 |
Patient 1, 0 h against 48 h |
| GSM798926 |
Patient 14, 0 h, in vivo |
| GSM798927 |
Patient 9, 0 h, in vivo |
| GSM798928 |
Patient 9, 48 h, in vivo |
| GSM798929 |
Patient 2, 0 h, in vivo |
| GSM798930 |
Patient 13, 48 h, in vivo |
| GSM798931 |
Patient 7, 48 h, in vivo |
| GSM798932 |
HL60, 0 h against 48 h 1mM VPA |
| GSM798933 |
Patient 17, 72 h, in vivo |
| GSM798934 |
Patient 11, 0 h, in vivo |
| GSM798935 |
Patient 16, 0 h, in vivo |
| GSM798936 |
Patient 13, 0 h, in vivo |
| GSM798937 |
Patient 11, 48 h, in vivo |
| GSM798938 |
Patient 5, 0 h, in vivo |
| GSM798939 |
Patient 4, 24 h, in vivo |
| GSM798940 |
Patient 17, 0 h, in vivo |
| GSM798941 |
Patient 3, 0 h, in vivo |
| GSM798942 |
K562, 0 h against 48 h 1mM VPA |
| GSM798943 |
Patient 15, 0 h, in vivo |
| GSM798944 |
Patient 18, 48 h, in vivo |
| GSM798945 |
Patient 12, 48 h, in vivo |
| GSM798946 |
Patient 5, 24 h, in vivo |
| GSM798947 |
Patient 15, 48 h, in vivo |
| GSM798948 |
Patient 6, 0 h, in vivo |
| GSM798949 |
Patient 8, 0 h, in vivo |
| GSM798950 |
Patient 1, 0 h, in vivo |
| GSM798951 |
Patient 3, 48 h, in vivo |
| GSM798952 |
Patient 7, 0 h, in vivo |
| GSM798953 |
Patient 12, 0 h, in vivo |
| GSM798954 |
Patient 2, 48 h, in vivo |
| GSM798955 |
NB4, 0 h against 48 h 1mM VPA |
| GSM798956 |
Patient 10, 48 h, in vivo |
| GSM798957 |
Patient 16, 48 h, in vivo |
| GSM798958 |
Patient 14, 48 h, in vivo |
| GSM798959 |
Patient 8, 48 h, in vivo |
| GSM798960 |
Patient 10, 0 h, in vivo |
| GSM798961 |
Patient 6, 72 h, in vivo |
| GSM798962 |
Patient 2, 24 h, in vitro |
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| Relations |
| BioProject |
PRJNA147191 |
| Supplementary data files not provided |
| Processed data included within Sample table |
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