Circulating CD133+/–CD34– Have Increased c- Expression in Myeloproliferative Neoplasms.

Objective: Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell (HSC)-originated diseases with clonal myeloproliferation. The constitutive activation of the JAK/STAT pathway is frequently detected in patients with Philadelphia chromosome-negative (Ph–) MPNs with an acquired V617F mutation. The c- proto-oncogene is associated with malignant growth and cellular transformation, and V617F was previously shown to induce constitutive expression of c-. This study examines the expressional profile of c- in Ph– MPNs with V617F 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) or V617F mRNA gold nanoparticle technology and sorted simultaneously. Isolated populations of wt or V617F were evaluated for their c- expressions. The MNCs of 14 Ph– MPNs were further isolated for the study of HSPC subgroups regarding their CD34 and CD133 expressions, evaluated for the presence of V617F, and compared to cord blood (CB) counterparts for the expression of c-.

Results: The mRNA-labeled gold nanoparticle-treated MNCs were determined to have the highest ratio of c- relative fold-change expression in the biallelic V617F compartment compared to JAK2wt. The relative c- expression in MNCs of MPNs was significantly increased compared to CB (p=0.01). The circulating HSPCs of CD133CD34 MPNs had statistically significantly elevated c- expression compared to CB.

Conclusion: This is the first study of circulating CD133CD34 cells in Ph– MPNs and it has revealed elevated c- expression levels in HSCs/endothelial progenitor cells (HSCs/EPCs) and EPCs. Furthermore, the steady increase in the expression of c- within MNCs carrying no mutations and monoallelic or biallelic V617F transcripts was notable. The presence of V617F with respect to c- expression in the circulating HSCs/EPCs and EPCs of MPNs might provide some evidence for the initiation of V617F and propagation of disease. Further studies are needed to clarify the implications of increased c- expression in such populations.