{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:24:00Z","timestamp":1747185840982,"version":"3.40.5"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2014\/14\/M\/NZ5\/00441"],"award-info":[{"award-number":["2014\/14\/M\/NZ5\/00441"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Out of <jats:italic>BCR\u2010ABL<\/jats:italic> negative myeloproliferative neoplasm (MPNPh<jats:sup>\u2212<\/jats:sup>) patients, 3%\u201314% display a concomitant monoclonal gammopathy of unknown significance (MGUS). In most cases, the diagnosis of plasma cell dyscrasia is either synchronous with that of MPNPh<jats:sup>\u2212<\/jats:sup> or occurs later on. We present a 50\u2010year\u2010old patient with type 2 <jats:italic>CALR<\/jats:italic> Lys385Asnfs*47 mutation positive essential thrombocythemia (ET) who developed symptomatic multiple myeloma (MM) 13 years after the diagnosis of ET during PEG\u2010INF2\u03b1 treatment. The NGS study performed at the time of the MM diagnosis revealed the HRAS Val14Gly\/c.41T\u232aG mutation and the wild type <jats:italic>CALR<\/jats:italic>, JAK2 and MPL gene sequence. In the presented case, the complete molecular remission of ET was achieved after 16 months of PEG\u2010INF2\u03b1 treatment. The origin of MM cells in MPNPh<jats:sup>\u2212<\/jats:sup> patients remains unknown. Published data suggests that type 2 CALRins5 up\u2010regulate the ATF6 chaperone targets in hematopoietic cells and activate the inositol\u2010requiring enzyme 1\u03b1\u2010X\u2010box\u2010binding protein 1 pathway of the unfolded protein response (UPR) system to drive malignancy. It cannot be excluded that endoplasmic reticulum stress induced by the increased ATF6 resulted in an abnormal redox homeostasis and proteostasis, which are factors linked to MM. The presented case history and the proposed mechanism of mutant <jats:italic>CALR<\/jats:italic> interaction with UPR and\/or ATF6 should initiate the discussion about the possible impact of the mutant <jats:italic>CALR<\/jats:italic> protein on the function and genomic stability of different types of myeloid cells, including progenitor cells.<\/jats:p>","DOI":"10.1111\/jcmm.17647","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T08:20:36Z","timestamp":1672993236000},"page":"299-303","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>HRAS<\/i> mutation positive multiple myeloma in the type 2 <i>CALR<\/i> mutation positive essential thrombocythemia: A case 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