AJH: PD-L1 overexpression is associated with JAK2-V617F mutational burden and with 9p uniparental disomy in myeloproliferative neoplasms.

Myeloproliferative neoplasm (MPN) is a chronic stem cell disease characterized by enhanced proliferation of myeloid cells, immune dysregulation, and drug resistance
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Somatic mutations in JAK2 cause disease in 50-60% of cases and CALR mutations in 25-30% of cases

Myeloproliferative neoplasm (MPN) is a chronic stem cell disease characterized by enhanced proliferation of myeloid cells, immune dysregulation, and drug resistance

Figure 1: RNA-sequencing shows upregulation of PD-L1 expression in myeloid cells from patients with polycythemia vera and the role of chromosome 9pUPD in the upregulation of PD-L1 expression in MPNs
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Figure 1: RNA-sequencing shows upregulation of PD-L1 expression in myeloid cells from patients with polycythemia vera and the role of chromosome 9pUPD in the upregulation of PD-L1 expression in MPNs
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Figure 1: RNA-sequencing shows upregulation of PD-L1 expression in myeloid cells from patients with polycythemia vera and the role of chromosome 9pUPD in the upregulation of PD-L1 expression in MPNs

By RNA-sequencing of granulocytes from 113 MPN patients, we found that PD-L1 expression was highest in polycythemia vera patients and that PDL1 expression correlated with JAK2-V617F mutational burden (R=0.

Figure 2: Evaluation of germline genetic variation at PD-L1 loci
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Figure 2: Evaluation of germline genetic variation at PD-L1 loci
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Figure 2: Evaluation of germline genetic variation at PD-L1 loci

Figure 3: PD-L1 is upregulated on the surface of stem cells isolated from bone marrow samples of MPN patients and downregulated by ruxolitinib and dBET6
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Figure 3: PD-L1 is upregulated on the surface of stem cells isolated from bone marrow samples of MPN patients and downregulated by ruxolitinib and dBET6
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Figure 3: PD-L1 is upregulated on the surface of stem cells isolated from bone marrow samples of MPN patients and downregulated by ruxolitinib and dBET6

Furthermore, haplotype-based association analysis provided evidence for germline genetic factors at the PD-L1 locus that contribute to MPN susceptibility independently of previously described GGCC risk haplotypes

Collectively, our data suggest that PD-L1 is abundantly expressed in MPN cells, including CD34+CD45dimCD38−NSCs defined by the MPN priming phenotype

Original source:

Original source:

Milosevic Feenstra JD, Jäger R, Schischlik F, Ivanov D, Eisenwort G, Rumi E, Schuster M, Gisslinger B, Machherndl-Spandl S, Bettelheim P, Krauth MT, Keil F, Bock C, Cazzola M, Gisslinger H, Kralovics R , Valent P.

Milosevic Feenstra JD, Jäger R, Schischlik F, Ivanov D, Eisenwort G, Rumi E, Schuster M, Gisslinger B, Machherndl-Spandl S, Bettelheim P, Krauth MT, Keil F, Bock C, Cazzola M, Gisslinger H, Kralovics R , Valent P.

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