Protein landscape in acute myeloid leukemia reveals proteins susceptible for drug discovery

ABSTRACT: Acute myeloid leukemia (AML) is a devastating cancer affecting the hematopoietic system. Although this disease represents only 35% of diagnosed leukemias, it accounts for nearly 50% of leukemia-related deaths, making it the leading cause of leukemia-related mortality. Although many AML initiating mutations have been identified, the downstream effects leading to disease progression are still largely unknown. Previous research has relied on RNA sequencing and microarray techniques to study the downstream effects, providing data at the transcriptional level. While these studies have proven efficacious, they fail to capture the changes that occur at the proteomic level. To interrogate the effect of protein expression alterations in AML, we performed a quantitative mass spectrometry analysis using mouse models to compare three tumor types to untransformed tumor-initiating population. In parallel, we performed RNA sequencing for the same populations. With these combined results, we identified 34 proteins whose expression was upregulated in AML tumors, but strikingly, were unaltered at the transcriptional level. These proteins are shown to be associated with mitochondrial function as well as RNA processing. These studies identify a set of proteins not previously associated with leukemia, and may ultimately serve as potential targets for therapeutic manipulation.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Spleen, Leukocyte

DISEASE(S): Acute Myeloid Leukemia

SUBMITTER: Samantha Swenson  

LAB HEAD: Shannon Mychel Buckley

PROVIDER: PXD025628 | Pride | 2022-05-20

REPOSITORIES: Pride