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| Status |
Public on Feb 05, 2018 |
| Title |
pre-B cells from normal control, preleukemic, fully leukemic and fully leukemic, nilotinib-treated P190 BCR/ABL transgenic mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) can be subdivided into different categories based on genetic abnormalities.
One type of pre-B ALL is characterized by the presence of the Philadelphia (Ph) chromosome, the derivative chromosome 22 that is one product of a reciprocal translocation between chromosomes 22 and 9. The 22/9 translocation fuses the 5’ part of the BCR gene to the 3’ end of the c-ABL gene. The resulting BCR/ABL fusion encodes a Bcr/Abl protein with deregulated Abl kinase activity. Two major fusion proteins are found in Ph-positive leukemias which differ in molecular weight and the size of the Bcr moiety. The P190 Bcr/Abl protein is common in Ph-positive ALL. Targeted tyrosine kinase inhibitors such as nilotinib are used therapeutically to treat this type of leukemia.
The 22/9 translocation fuses the 5’ part of the BCR gene to the 3’ end of the c-ABL gene.
The resulting BCR/ABL fusion encodes a Bcr/Abl protein with deregulated Abl kinase activity. Two major fusion proteins are found in Ph-positive leukemias which differ in molecular weight and the size of the Bcr moiety.
The P190 Bcr/Abl protein is common in Ph-positive ALL. Targeted tyrosine kinase inhibitors such as nilotinib are used therapeutically to treat this type of leukemia.
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| Overall design |
Mice transgenic for the human P190 form of Bcr/Abl (Jackson Labs strain 017833) develop precursor B-lineage (pre-B) acute lymphoblastic leukemia, on average within 3 months of birth, when on a C57Bl/6J background. Bone marrows were isolated from control C57BLl/6J mice and from transgenic Bcr/Abl mice when they had not yet developed full-blown leukemia (<60 days of age), from Bcr/Abl transgenic mice with overt leukemia and packed bone marrows (>90 days of age), and from fully leukemic mice that had received a seven-day treatment with 75 mg/kg AMN107 (nilotinib). Three mice were used per condition, and cells from each mouse were processed separately. Pre-B cells from these twelve bone marrows were flow-sorted using CD19 and AA4.1 as markers. Total RNA from CD19+ AA4.1+cells used for microarray analysis was isolated by RNeasy (QIAGEN) purification. Double-strand complementary DNA was generated from 5 µg of total RNA using a poly(dT) oligonucleotide that contains a T7 RNA polymerase initiation site and the SuperScript III reverse transcription (Invitrogen). Biotinylated cRNA was generated and fragmented according to the Affymetrix protocol and hybridized to 430 mouse microarrays (Affymetrix).
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| Contributor(s) |
Heisterkamp NC, Kaur P, Trageser D, Klemm L, Muschen M |
| Citation(s) |
19620627, 33878293 |
| |
| Submission date |
Feb 04, 2018 |
| Last update date |
Jul 07, 2021 |
| Contact name |
Nora Heisterkamp |
| E-mail(s) |
eheisterkamp@coh.org
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| Phone |
626-218-7503
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| Organization name |
Beckman Research Institute City of Hope
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| Department |
Department of Systems Biology
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| Street address |
1218 S Fifth Avenue
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| City |
Monrovia |
| State/province |
CA |
| ZIP/Postal code |
91016 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (12)
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| GSM2977664 |
[mouse BM][preleukemic CD19+AA4.1+][1] |
| GSM2977665 |
[mouse BM][preleukemic CD19+AA4.1+][2] |
| GSM2977666 |
[mouse BM][preleukemic CD19+AA4.1+][3] |
| GSM2977667 |
[mouse BM][leukemic CD19+AA4.1+][1] |
| GSM2977668 |
[mouse BM][leukemic CD19+AA4.1+][2] |
| GSM2977669 |
[mouse BM][leukemic CD19+AA4.1+][3] |
| GSM2977670 |
[mouse BM][leukemic CD19+AA4.1+ nilotinib treated][1] |
| GSM2977671 |
[mouse BM][leukemic CD19+AA4.1+ nilotinib treated][2] |
| GSM2977672 |
[mouse BM][leukemic CD19+AA4.1+ nilotinib treated][3] |
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| Relations |
| BioProject |
PRJNA432848 |
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