Circulating CD133+/- CD34- progenitors have increased c-MYC expressions in Myeloproliferative Neoplasms.

Objective
Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell (HSC)-originated diseases with clonal myeloproliferation. The constitutive activation of JAK/STAT pathway is frequently detected in patients with Philadelphia chromosome negative (Ph-) MPNs with an acquired mutation JAK2V617F. Proto-oncogene, c-MYC is associated with malignant growth and cellular transformation, and previously, JAK2V617F has been shown to induce a constitutive expression of c-MYC. This study examines the expressional profile of c-MYC in Ph-MPNs with JAK2V617F and highlights its hierarchical level of activation in circulating hematopoietic stem/progenitor cell (HSPC) subgroups.


Materials and Methods
Mononuclear cells(MNCs) of Ph-MPNs were fluorochrome-labeled in situ with wild-type(wt)-JAK2 or JAK2V617F mRNA gold nanoparticle technology and sorted simultaneously. The isolated populations of JAK2wt or JAK2V617F were evaluated for their c-MYC expressions. MNCs of fourteen Ph-MPNs were further isolated for HSPC subgroups regarding to their CD34 and CD133 expressions, evaluated for the presence of JAK2V617F, and compared to cord blood (CB) counterparts for the expression of c-MYC.


Results
The mRNA-labeled gold nanoparticle-treated MNCs were determined to have the highest ratio of c-MYC relative fold-change expression in biallelic-JAK2V617F compartment compared to JAK2wt. The relative c-MYC expression in MNCs of MPN revealed significant increase compared to CB(p=0.01). The circulating HSPC of MPN in CD133+/-CD34- have revealed a statistically significant elevated c-MYC expression compared to CB.


Conclusion
This is the first study of circulating CD133+/-CD34- in Ph-MPNs, and reveals an elevated c-MYC expression level in the HSC/endothelial progenitor cells (HSC/EPC) and EPC. Furthermore, the steady increase in the expression of c-MYC within the MNCs carrying no mutation, monoallelic, or biallelic-JAK2V617F transcripts was notable. The presence of JAK2V617F with respect to c-MYC expression in the circulating in HSC/EPC and EPC of MPN might provide some evidence for the initiation of JAK2V617F and propagation of disease. Further studies are required to highlight the implication of increased c-MYC expression in such populations.