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| Status |
Public on Aug 05, 2015 |
| Title |
Germline duplication of ATG2B and GSKIP predisposes to familial essential thrombocythemia rapidly progressing to acute leukemia |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by array
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| Summary |
No major predisposing gene for familial myeloproliferative neoplasms (MPN) has been identified. Here, we demonstrate that the autosomal dominant transmission of a 700 kb duplication in four geographically-related families predisposes to MPN rapidly progressing to acute leukemia. Using induced pluripotent stem and primary cells to explore hematopoietic differentiation, we demonstrate that overexpressed ATG2B and GSKIP enhance hematopoietic progenitor differentiation, including megakaryocytic through increasing their sensitivity to TPO. ATG2B and GSKIP cooperate with acquired JAK2, MPL and CALR mutations during MPN development. Thus, the germline duplication changes the fitness of cells harboring signaling mutations and increases the probability of disease development.
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| Overall design |
14 samples corresponding to iPSC and control cases (Cy5) where hybridized in dual color against commercial normal reference DNA (Cy3) of matched sex, except for samples with unknown gender for which male normal was used as reference.
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| Contributor(s) |
Saliba J, Saint-Martin C, Di Stefano A, Lenglet G, Marty C, Keren B, Pasquier F, Della Valle V, Secardin L, Leroy G, Mahfoudhi E, Grosjean S, Droin N, Diop KM, Charrier S, Palazzo A, Merlevede J, Mediane J, Delaunay-Darivon C, Fuseau P, Isnard F, Casadevall N, Solary E, Debili N, Bernard OA, Raslova H, Najman A, Vainchenker W, Bellanné-Chantelot C, Plo I |
| Citation missing |
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| Submission date |
Apr 15, 2015 |
| Last update date |
Mar 21, 2017 |
| Contact name |
Bastien Job |
| E-mail(s) |
bastien.job@gustaveroussy.fr
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| Phone |
+330142114211
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| Organization name |
Institut Gustave Roussy
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| Lab |
Bioinformatics Core Facility
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| Street address |
39 rue Camille Desmoulins
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| City |
VILLEJUIF |
| ZIP/Postal code |
94800 |
| Country |
France |
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| Platforms (1) |
| GPL9777 |
Agilent-021850 SurePrint G3 Human CGH Microarray (Feature Number version) |
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| Samples (14)
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| GSM1659018 |
Control IPSC clone b |
| GSM1659019 |
IPSC JAK2V617F clone b |
| GSM1659020 |
IPSC predisposition +JAK2V617F+TET2 mutation clone b |
| GSM1659021 |
IPSC predisposition +JAK2V617F clone b |
| GSM1659022 |
IPSC predisposition only clone b |
| GSM1659023 |
Control progenitors |
| GSM1659024 |
Progenitors from JAK2V617F sporadic patient |
| GSM1659025 |
Progenitors from patient with predisposition JAK2V617F and TET2 mutation |
| GSM1659026 |
Progenitors from patient with predisposition only |
| GSM1659027 |
IPSC JAK2V617F clone a |
| GSM1659028 |
IPSC predisposition +JAK2V617F+TET2 mutation clone a |
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| Relations |
| BioProject |
PRJNA281252 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE67938_RAW.tar |
609.6 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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