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. 2023 Aug;102(2):168-178.
doi: 10.1111/tan.15026. Epub 2023 Apr 1.

Exploration of the role of NKG2D ligands MICA and MICB in JAK2 V617F-positive myeloproliferative neoplasms

Milena Ivanova  1 , Gergana Tsvetkova  2 , Spaska Lessichkova  1 , Nevena Gesheva  1 , Evgueniy Hadjiev  2 , Velizar Shivarov  3
Affiliations

Exploration of the role of NKG2D ligands MICA and MICB in JAK2 V617F-positive myeloproliferative neoplasms

Milena Ivanova et al. HLA. 2023 Aug.

Abstract

JAK2 V617F-driven myeloproliferative neoplasms (MPNs) can escape immune surveillance through PD-L1 up-regulation and HLA class I pathway down-regulation. To complement these data we assessed the role of major histocompatibility complex class I-related genes (MICA and MICB) in JAK2 V617F+ MPNs. Using high resolution genotyping we identified two protective alleles, MICA*008:01 and MICA*016. MPN patients had significantly higher levels of soluble sMICA molecules. Peripheral blood JAK2 V617F+ granulocytes had higher surface expression of MICB but did not differ in the amount of MICA and MICB transcripts from normal granulocytes. MICA and MICB genes were significantly down-regulated in JAK2 V617F+ CD34+ cells from primary myelofibrosis patients in comparison to normal CD34+ hematopoietic stem cells. These data suggest minor but significant role of MICA and MICB genes in the pathogenesis of MPNs. It is also possible that MICA targeting approaches could be of clinical benefit for some of those patients.

Keywords: JAK2 V617F; MICA; MICB; NKG2D; immune evasion.

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References

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