RNA-sequencing, tandem-mass-tag (TMT) proteomics, label-free-quantification (LFQ) proteomics, and TurboID proximity labeling experimental data from a study of murine acute myeloid leukemia (AML) that spontaneously develops in mice with Dnmt3aR878H/+ x Npm1cA/+ bone marrow. These mice spontaneously develop myelomonocytic AML in 6-15 months. We characterized pre-leukemic bone marrow samples, and 11 independent spontaneous AMLs that developed in these doubly-mutant mice ("mAML1-11").10 of 11 AMLs contained an amplification of murine chromosome 7 (chr7), usually as the only structural variant. Furthermore, we identified two non-leukemic mice where whole genome sequencing revealed amplification of chromosome 7 (+7) and no other cooperating mutations in identifiable driver genes (pre-tumor, +7 only). One of these clonal expansions was tested twice in secondary transplant assays, and did not commonly yield fatal disease when transplanted into recipients, suggesting that +7 is an intermediate step in AML progression. Further experiments identified Gab2 as an important gene on chromosome 7 for AML pathogenesis in this model. Retroviral overexpression of Gab2 in Dnmt3aR878H/+ x Npm1cA/+ bone marrow led to expansion of bone marrow cells both in vitro and in vivo in transplanted, recipient mice, as well as to accelerated development of AML; the resulting AML samples are called GAB2 mAML in this dataset. RNA sequencing and proteomics measurements were performed from bulk bone marrow of mice.
Proximity labeling experiments were performed using the TurboID system to label intracellular proteins that are in close proximity to the GAB2, NPM1wt, NPM1cA, DNMT3Awt or DNMT3AR882H proteins ("baits") in primary murine HSPCs. We used a TurboID cDNA fused in-frame to the N- or C-terminus of each bait in an MSCV-based retroviral vector, and transduced these vectors into primary murine bone marrow HSPCs from relevant genotypes (wild-type, Dnmt3aR878H/+, or Dnmt3aR878H/+ x Npm1cA). TurboID cDNA alone was used as a control for non-specific biotin labeling. Biotin-labeled proteins were pulled down with streptavidin and then identified using mass-spectrometry. Spectral counts (normalized to counts per 10,000) were used to measure protein abundance as a measure of proximity to the tagged protein.
Data are available freely for download and use. Please refer to the following paper for further information and please cite this paper for any use of these data:
Kramer MH, Richardson SN, Li Y, Yin T, Helton NM, George DR, Cai M, Ramakrishnan SM, Katerndahl CDS, Miller CA, Ley TJ. Overexpression of the signaling-coordinator GAB2 can play an important role in Acute Myeloid Leukemia progression. The Journal of Clinical Investigation. 2025. doi: 10.1172/JCI195929
Raw mass spectrometry data is deposited in the MassIVE database (MSV000097966 [TurboID], MSV000098719 [TMT], MSV000098728 [LFQ]).
Download links:
Download the RNA seq abundance data