{"title":"Downregulation of autophagy is associated with poor clinical outcome after immunochemotherapy in patients with diffuse large B-cell lymphoma","authors":"Ya-Li Zhang , Meng-Xue Ma , Li-Na Xing , Jing-Nan Zhang , Xiao-Nan Guo , Shu-kai Qiao","doi":"10.1016/j.exphem.2024.104638","DOIUrl":"10.1016/j.exphem.2024.104638","url":null,"abstract":"<div><div>This study aimed to determine the expression levels of the autophagy markers Beclin-1 and p62 in patients with diffuse large B-cell lymphoma (DLBCL) and explore the association between autophagy and disease prognosis. The expression of Beclin-1 and p62 was investigated in patients with DLBCL and patients with reactive lymphoproliferative disease (RLD) using immunohistochemistry. The association between the clinical characteristics of patients with DLBCL and autophagy status was further analyzed. Beclin-1 levels were increased in RLD patients compared with those with DLBCL, but the difference was not statistically significant (<em>p</em> > 0.05). p62 levels in DLBCL patients were significantly higher than those in RLD patients (<em>p</em> < 0.05). Beclin-1 expression was associated only with the Ann Arbor stage (<em>p</em> < 0.05), whereas p62 expression was associated with the Ann Arbor stage, IPI score, extranodal involvement, and Ki-67 index (<em>p</em> < 0.05). Beclin-1 and p62 levels were not associated with short-term treatment efficacy in DLBCL patients. Survival analysis showed that Beclin-1 expression had no significant effect on 2-year progression-free survival (PFS) or overall survival (OS) (<em>p</em> > 0.05). However, high p62 expression in DLBCL patients was associated with reduced 2-year PFS compared with that of patients with low p62 expression (<em>p</em> < 0.05); the 2-year OS was not affected (<em>p</em> > 0.05). Our results demonstrate that autophagic activity affects the prognosis of DLBCL patients; the lower the autophagic activity, the shorter the PFS. Targeted p62 knockout may be a novel therapeutic strategy for the treatment of DLBCL patients.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"139 ","pages":"Article 104638"},"PeriodicalIF":2.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Involvement of CREB3L1 in erythropoiesis induced by JAK2 exon 12 mutation","authors":"Maho Okuda , Marito Araki , Federico De Marchi , Soji Morishita , Misa Imai , Hanaka Fukada , Miki Ando , Norio Komatsu","doi":"10.1016/j.exphem.2024.104636","DOIUrl":"10.1016/j.exphem.2024.104636","url":null,"abstract":"<div><div><em>CREB3L1</em>, a gene encoding the endoplasmic reticulum stress transducer, is specifically overexpressed in platelet RNA from patients with myeloproliferative neoplasms (MPNs). However, the pathophysiological roles of <em>CREB3L1</em> overexpression remain unclear. In the present study, we aimed to study <em>CREB3L1</em> messenger RNA (mRNA) expression in the red blood cells (RBCs) of patients with MPN and its role in erythrocytosis. Elevated expression of <em>CREB3L1</em> was exclusively observed in the RBCs of patients with polycythemia vera (PV) harboring <em>JAK2</em> exon 12 mutations, but not in those harboring <em>JAK2</em> V617F mutation or control subjects. In erythropoiesis, <em>CREB3L1</em> expression was sharply induced in erythroblasts of bone marrow cells collected from patients with <em>JAK2</em> exon 12 mutation. This was also evident when erythropoiesis was induced in vitro using hematopoietic stem and progenitor cells (HSPCs) with <em>JAK2</em> exon 12 mutation. Interestingly, overexpression of <em>CREB3L1</em> in RBCs was observed in patients with reactive erythrocytosis whose serum erythropoietin (EPO) levels exceeded 100 mIU/mL. Elevated <em>CREB3L1</em> expression was also observed in the erythroblasts of a patient with acute erythroid leukemia. EPO-dependent induction of <em>CREB3L1</em> was evident in erythroblasts differentiated from HSPCs in vitro, regardless of driver mutation status or MPN pathogenesis. These data strongly suggest that <em>CREB3L1</em> overexpression in RBCs is associated with hyperactivation of the EPO receptor and its downstream molecule, JAK2. Short hairpin RNA (shRNA) knockdown of <em>CREB3L1</em> expression in HSPCs blocked erythroblast formation in vitro. These results suggest that <em>CREB3L1</em> is required for erythropoiesis in the presence of <em>JAK2</em> exon 12 mutation or high level of EPO, possibly by antagonizing cellular stress.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"139 ","pages":"Article 104636"},"PeriodicalIF":2.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charlotta Böiers, Ariana Calderón, Roshanak Ghazanfari, Shabnam Khazari, Stefan Lang, Mohamed Eldeeb, Sara Palo, Shamit Soneji, David Bryder, Charlotta Böiers
{"title":"3216 – FORMATION OF PRE-LEUKEMIC STEM CELLS IN A KMT2A::AFF1 MURINE MODEL REQUIRES AN EMBRYONIC TARGET CELL","authors":"Charlotta Böiers, Ariana Calderón, Roshanak Ghazanfari, Shabnam Khazari, Stefan Lang, Mohamed Eldeeb, Sara Palo, Shamit Soneji, David Bryder, Charlotta Böiers","doi":"10.1016/j.exphem.2024.104536","DOIUrl":"https://doi.org/10.1016/j.exphem.2024.104536","url":null,"abstract":"","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"10 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LaShanale Wallace, Mark Engelken, Amina Metidji, Jacquelyn Myers, Heather Sheppard, Jeremy Crawford, John Harper, David Cullins, Paul Thomas, Esther Obeng
{"title":"3194 – CLONAL HEMATOPOIESIS-ASSOCIATED DNMT3A MUTATIONS CAUSE INCREASED T CELL ACTIVATION AND DECREASED LEUKEMIC TUMOR BURDEN","authors":"LaShanale Wallace, Mark Engelken, Amina Metidji, Jacquelyn Myers, Heather Sheppard, Jeremy Crawford, John Harper, David Cullins, Paul Thomas, Esther Obeng","doi":"10.1016/j.exphem.2024.104514","DOIUrl":"https://doi.org/10.1016/j.exphem.2024.104514","url":null,"abstract":"","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"28 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}