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| Status |
Public on May 24, 2016 |
| Title |
Affymetrix SNP array data for myelodysplastic syndromes samples |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
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| Summary |
Traditional response criteria in MDS and AML are based on bone marrow morphology and may not accurately reflect tumor burden in patients treated with hypomethylating agents. We used massively parallel sequencing of serial bone marrow samples to monitor MDS and AML tumor burden during treatment with epigenetic therapy (decitabine and panobinostat). Serial bone marrow samples (and skin as a source of normal DNA) from 25 MDS and AML patients were sequenced . We observed that responders, including those in complete remission (CR), can have persistent measurable tumor burden for at least one year without disease progression. Using an ultra-sensitive barcode sequencing approach, we detected extremely rare mutations months to years prior to disease relapse. While patients can live with persistent clonal hematopoiesis in a CR or stable disease, ultimately we find evidence that expansion of a rare subclone can drive relapse or progression. Digital sequencing provides an alternative measure of tumor burden and disease response which may augment traditional clinical response criteria in patients treated with hypomethylating agents and its use should be explored in future clinical trials.
BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. The Philadelphia chromosome, encoding BCR-ABL1, is the defining lesion of chronic myelogenous leukemia (CML) and a subset of acute lymphoblastic leukemia (ALL) cases. To define oncogenic lesions that cooperate with BCR-ABL1 to induce ALL, we performed genome-wide analysis of leukemic samples from 23 CML cases and 304 ALL cases, including 43 BCR-ABL1 B-ALL cases. IKZF1 (encoding the transcription factor Ikaros) was deleted in 83.7% of BCR-ABL1 B-ALL cases, but not in chronic phase CML. Deletion of IKZF1 was also identified as an acquired lesion in lymphoid blast crisis of CML. The IKZF1 deletions resulted in haploinsufficiency, expression of a dominant negative Ikaros isoform or the complete loss of Ikaros expression. Sequencing of IKZF1 deletion breakpoints suggested that aberrant V(D)J recombination is responsible for the deletions. These findings suggest that genetic lesions resulting in the loss of Ikaros function are a key event in the development of BCR-ABL1 ALL.
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| Overall design |
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or skin tissue samples.
Copy number analysis of Affymetrix genome wide SNP 6.0 arrays was performed for MDS 7 patients, each patient has skin, bone marrow tumor at pre-study and last. skin DNA was used as references for copy number inference (therefore there are only 14 data columns in the processed data file; no processed data for the skin samples).
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| Contributor(s) |
Uy GL, Duncavage EJ, Shao J, Walter MJ |
| Citation missing |
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| Submission date |
May 23, 2016 |
| Last update date |
Nov 27, 2018 |
| Contact name |
Matt Walter |
| E-mail(s) |
mjwalter@dom.wustl.edu
|
| Organization name |
washington university in st.louis school of medicine
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| Department |
oncology
|
| Street address |
4940 parkview
|
| City |
st.louis |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (1) |
| GPL6801 |
[GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA322462 |
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