Abstract

Megakaryocytes are considered to be drivers of disease biology in the Philadelphia-negative myeloproliferative neoplasms. Yet, a proteomic characterization of these cells is lacking due to sparse numbers in the bone marrow and the disruption of bone marrow architecture in myeloproliferative neoplasms. Transcriptomic studies have been conducted on megakaryocytes differentiated from peripheral blood hematopoietic stem cells, and any effect of the highly disrupted bone marrow microenvironment on gene expression of megakaryocytes is lost. This study takes an unbiased low-input spatial proteomics approach to study in vivo megakaryocytes in myeloproliferative neoplasms for the first time. 

Highlights

- A novel workflow for low-input spatial proteomics combining immunohistochemistry, artificial intelligence–based image analysis, and laser capture microscopy.

- The first mass spectrometry–based proteomic study of in vivo–differentiated megakaryocytes in humans.

- The first study to confirm that megakaryocytes have disease-specific proteomic signatures in classical Philadelphia-negative myeloproliferative neoplasms.