{"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, Shukai Qiao","doi":"10.1016/j.exphem.2024.104638","DOIUrl":"https://doi.org/10.1016/j.exphem.2024.104638","url":null,"abstract":"<p><p>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 (n=60) and patients with reactive lymphoproliferative disease (RLD; n=20) using immunohistochemistry. The association between the clinical characteristics of patients with DLBCL and autophagy status was further analyzed. Beclin-1 levels were increased in patients with RLD compared to those with DLBCL, but the difference was not statistically significant (P>0.05). p62 levels in patients with DLBCL were significantly higher than those in patients with RLD (P<0.05). Beclin-1 expression was associated only with the Ann Arbor stage (P<0.05), whereas p62 expression was associated with the Ann Arbor stage, International Prognostic Index score, extranodal involvement, and Ki-67 index (P<0.05). Beclin-1 and p62 levels were not associated with short-term treatment efficacy in patients with DLBCL. Survival analysis showed that Beclin-1 expression had no significant effect on 2-year progression-free survival (PFS) or overall survival (OS) (P>0.05). However, high p62 expression in patients with DLBCL was associated with reduced 2-year PFS compared with that of patients with low p62 expression (P<0.05); the 2-year OS was not affected (P>0.05). Our results demonstrate that autophagic activity affects the prognosis of patients with DLBCL; the lower the autophagic activity, the shorter the PFS. Targeted p62 knockout may be a novel therapeutic strategy for the treatment of patients with DLBCL.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":null,"pages":null},"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":"","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":"https://doi.org/10.1016/j.exphem.2024.104636","url":null,"abstract":"<p><p>CREB3L1, 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 CREB3L1 overexpression remain unclear. In the present study, we aimed to study CREB3L1 mRNA expression in the red blood cells (RBCs) of patients with MPN and its role in erythrocytosis. Elevated expression of CREB3L1 was exclusively observed in the RBCs of patients with polycythemia vera (PV) harboring JAK2 exon 12 mutations, but not in those harboring JAK2 V617F mutation or control subjects. In erythropoiesis, CREB3L1 expression was sharply induced in erythroblasts of bone marrow cells collected from patients with JAK2 exon 12 mutation. This was also evident when erythropoiesis was induced in vitro using hematopoietic stem and progenitor cells (HSPCs) with JAK2 exon 12 mutation. Interestingly, overexpression of CREB3L1 in RBCs was observed in patients with reactive erythrocytosis whose serum erythropoietin (EPO) levels exceeded 100 mIU/mL. Elevated CREB3L1 expression was also observed in the erythroblasts of a patient with acute erythroid leukemia. EPO-dependent induction of CREB3L1 was evident in erythroblasts differentiated from HSPCs in vitro, regardless of driver mutation status or MPN pathogenesis. These data strongly suggest that CREB3L1 overexpression in RBCs is associated with hyperactivation of the EPO receptor and its downstream molecule, JAK2. shRNA knockdown of CREB3L1 expression in HSPCs blocked erythroblast formation in vitro. These results suggest that CREB3L1 is required for erythropoiesis in the presence of JAK2 exon 12 mutation or high level of EPO, possibly by antagonizing cellular stress.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-03","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}
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":null,"pages":null},"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}
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":null,"pages":null},"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}