Programmed Cell Death Receptor (PD-1), PD-1 Ligand (PD-L1) Expression in Philadelphia Chromosome Negative Myeloid Neoplasms

Introduction : PD-1 and PD-L1 pathway inhibitor therapy has been extensively explored in the field of oncology treatment recently, however there is no information so far about its usefulness in myeloid neoplasms (MPN). We have previously reported on PD-1 and PD-L1 expression in Philadelphia chromosome negative myeloid neoplasm (MPN), but now that we have accumulated more cases , we wish to report the final results.

Materials and Methods: 63 patients with Philadelphia chromosome negative MPN in total were studied which included 16 MF (14 PMF, 2 post-PV-MF, 2 post-ET-MF), 29 ET, 18 PV, and 25 normal volunteer controls.

Flow CytometryStudies: Leukocytes were obtained from whole blood after RBC lysis using RBC lysis buffer (Qiagen). To quantify surface bound PD-1 and PDL-1, the leukocytes were incubated with CD279-APC and CD274-PE, as well as CD4-FITC, CD8-FITC, CD14-PCP, or CD34-FITC (BD Biosciences) and were subjected to flow cytometric analysis.

Results: PD-1 and PD-L1 positive cells were expressed as a percentage in gated CD4^bright, CD8⁺, CD14⁺, or CD34⁺ cells. We found that 1) there was no difference in PD-1 or PD-L1 levels among different groups of MPN, but there was a significant difference when they were grouped of PV, ET and MF as MPN and compared with controls in all the immune cells including CD4⁺, CD8⁺, CD14 ⁺ and,CD34⁺ cells.(Representative of CD4⁺ shown inFig(1a). 2) High expression levels (more than 50% cell positivity) was found on the CD34⁺ cells with PD-1 and PD-L1 expression of 20% and 26% in MPN patients respectively ( Fig 1b,1c) . 3) We also found that there was no correlation between of the PD-1 or , PD-L1 expression levels with clinical features including such as WBC counts , platelet counts, and hemoglobin levels, , or presence or absence of the JAK2 , MPL, or CALR gene mutations or splenomegaly

Conclusion: We have shown elevated increased expression levels of PD1 and PDL-1 on the immune cells and high expression ( more than 50%) in the CD34⁺ cells , suggest that PD-1 or , PD-L1 pathway inhibitor therapy maybe worthwhile in Philadelphia chromosome negative Ph(-) MPN ..

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