Abstract Objectives The Revised international prognostic scoring system (IPSS-R) is now commonly being used clinically to guide the treatment of myelodysplastic neoplasms (MDS). Recently, the Molecular International Prognostic Scoring System (IPSS-M)was proposed. In this study, we have validated the potential predictive value of the comparative IPSS-M in Chinese MDS patients. Design Retrospective multicenter observational study. Setting and participants 113 MDS patients(April 2019 - June 2022) from 10 distinct centers in Jiangnan region of China, grouped by IPSS-R and IPSS-M was obtained and the scoring criteria were retrospectively analyzed to compare the prognostic assessment efficacy of the different prognostic assessment systems. Main outcome measures The prognostic indicators of MDS patients are main outcome measures. Results 72 (63.7%) patients were reclassified after regrouping from IPSS-R to IPSS-M, and 52 of them were transferred to a higher risk group, with a higher percentage of patients aged ≥ 60 years in the higher risk group. Survival analysis confirmed that overall survival(OS) was variable in the different risk strata, with shorter survival time in the higher risk group and lower OS in the older(≥ 60 years) than in the younger group; whereas in univariate and multifactorial analysis, age ≥ 60 years, percentage of bone marrow blasts, chromosomal classification of IPSS-R, TP53, RUNX1, DNMT3A, NRAS, CBL, GNAS, and FLT3_ITD gene mutation were associated with OS. Leukemia-free survival(LFS)analysis revealed that higher IPSS-R and IPSS-M risk stratification was linked with shorter LFS time. Receiver operating characteristic (ROC) curves were drawn according to OS displaying AUC = 0.629 for IPSS-R and AUC = 0.705 for IPSS-M; AUC = 0.635 for IPSS-M younger group and AUC = 0.691 for older group. Conclusions Our study confirmed that the IPSS-M prognostic scoring system could be applicable to Chinese patients and that IPSS-M was significantly better than IPSS-R for the prognostic assessment of MDS patients. Moreover, IPSS-M appeared to have better predictive validity in older patients compared to younger patients.

Multiple myeloma (MM) is the second most common type of hematological malignancy globally. Despite application of several new drugs, such as daratumumab, bortezomib/lenalidomide/dexamethasone, in combination with hematopoietic stem cell transplantation, overall prognosis remains poor and the pathological mechanism of MM is still unknown. The present study used TargetScan to predict autophagy-related 7 (ATG7) as a candidate target gene of microRNA (miR)-1343-3p and confirmed the interaction between miR-1343-3p and the ATG7 3' untranslated region (3'UTR) using a dual-luciferase reporter assay. In U266 and RPMI-8226 MM cell lines, miR-1343-3p mimic transfection decreased mRNA and protein levels of ATG7, while miR-1343-3p inhibition increased ATG7 expression levels using reverse transcription-qPCR and western blot analysis. miR-1343-3p mimic transfection inhibited U266 and RPMI-8226 cell survival. Finally, miR-1343-3p regulated ATG7 and autophagy in MM cells using western blot analysis. The present findings suggested that miR-1343-3p may regulate ATG7 and autophagy by directly targeting the 3'UTR of ATG7. To the best of our knowledge, there are no direct data showing the roles of miR-1343-3p in development of MM; however, miR-1343-3p may be considered a potential target for MM treatment.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by decreased platelet (PLT) count in peripheral blood and bone marrow megakaryocyte dysfunction. The standard first-line treatment of newly diagnosed ITP was still corticosteroids (CIS), intravenous immunoglobulin (IVIG) or anti-D IG for those PLT≤30×109/L. According to the present international consensus or clinical guidelines, the timeline for cease or starting maintenance treatment (no more than 5mg daily) of CIS should within 6-8 weeks. However, many relapses happened practically, and need to switch into second line treatment such as thrombopoietin receptor agonist (TPO-RA). Eltrombopag (EPAG), the first oral non-peptide TPO-RA, achieved ~80% response in chronic ITP patients. The initial recommend dose of EPAG was 25mg according to Chinese Guideline, and the response rate increased if the daily dose increased to 50mg or 75mg (22.22%, 45.45 % and 65.52%, respectively), however the financial burden increased accordingly, especially for patients in developing country. It is of great clinical significance if we can invoke a treatment protocol that could gain all the benefits, including quick response, timely CIS withdrawal as well as high sustained response. Herein, we raise a multicenter phase 2 clinical trial, which aimed to explore the efficacy of low-dose corticosteroids (LD-CIS) plus low-dose eltrombopag (LD-EPAG) for newly diagnosed, treatment-naïve ITP patients. The study included three phases: 1) core treatment period (8 weeks), patients received fixed LD-CIS (weight≤ 50kg, 20 mg/d; weight> 50kg, 0.4 mg/kg/d) for 3 weeks and reduced gradually to target dosage within 8 weeks, with fixed LD-EPAG (25 mg daily) treatment; 2) decrement and discontinuation period (12 weeks): EPAG gradually tapered if the PLT count maintain above 100×109/L over 2/3 of the core treatment period; 3) follow-up period (6 months): LD-CIS and LD-EPAG ceased and observe the sustained response for 6 months. The primary endpoint was the ratio of CIS discontinuation or maintenance dose less than 5mg QD within 8 weeks with a PLT≥ 50×109/L. The secondary endpoint of study was durable response after EPAG discontinuation or maintenance dose ≤ 25mg BIW. Between July 2022 and March 2024, 16 centers participate in, and 41 patients from 5 centers were screened for eligibility. Sixteen cases were excluded, and 23 patients were ultimately enrolled and finished the whole study. 23 patients were ultimately enrolled and finished the whole study. The median age was 53.83 (range 23-88) years old. For efficacy assessment, all the patients achieved an increased PLT from baseline. The complete response (CR, PLT ≥ 100×109/L) was achieved in 60.87% (14/23) patients at the end of 2nd week observation, which increased to 84.21% (16/19) at the end of 12th weeks. As noted, the overall response rate (ORR) reached 100% in 2nd weeks and maintained above 90% throughout the study. The median intervals time required for platelet to reach 30×109/L and 100×109/L for the first time were 6 (2-18) and 14.5 (4-45) days, respectively. Out of 23 patients received our treatment protocol, 22 (95.65%) patients achieved the primary endpoint, except for one patient exhibited CIS-dependent. The secondary endpoint of study was the proportion of patients who achieved EPAG discontinuation or maintenance dose ≤ 25mg BIW until Week 20, which was 52.94% in 9 out of evaluable 17 patients, of which, 8 cases accomplished SRoT with a median durable response of 5.5 (range 2.75-5) months. In addition, the median bleeding score pretreatment was 2 (0-4), which was decreased at each point post-treatment by paired t-test. Clinical assessment of ITP commonly focusses on platelet counts and risk of bleeding, fatigue and HRQoL were also longitudinally evaluated in our cohort. The results showed that there were no significant differences in fatigue score after the combination therapy, while mental health (MH) score was improved. In addition, no severe adverse events were observed during the whole study, the treatment related side effect such as impaired glucose tolerance, liver dysfunction, etc. In summary, the combination of low-dose corticosteroids and eltrombopag can exert a quick and durable response in newly diagnosed ITP, and partly improve their quality of life. This regimen represents a potential first-line treatment, but further randomized controlled studies are needed to consolidate this conclusion.

Purpose: To detect JAK2 p.V617F and measure allele burden in peripheral blood (PB) and bone marrow (BM) aspirates in patients with suspected myeloproliferative neoplasms (MPNs). Methods: Patients with suspected MPNs were prospectively enrolled between August 2017 and May 2019, and their PB and BM were collected during the same period. Quantitative fluorescence polymerase chain reaction (PCR) was used to detect the copy number of JAK2 wild type and the V617F mutant; the JAK2 V617F proportion was also calculated. The JAK2 p.V617F proportion in PB was compared to that in BM by Chi-square test. Results: Among 54 patients with suspected MPNs, 43 of them were eligible for analysis. The JAK2 p.V617F in PB had the same sensitivity and specificity as BM (all P>0.05). The Chi-square test suggested that the JAK2 p.V617F allele burden of PB was comparable to that of BM (Spearman Cor-relation =0.986; P=0.000). Conclusion: PB could be used as an alternative to BM for JAK2 p.V617F measurement in patients with suspected MPNs.

Objective Several laboratory and imaging assays are required to diagnose multiple myeloma (MM). Serum and urine immunofixation electrophoresis are two key assays to diagnose MM, while they have not been extensively utilized in Chinese hospitals. Serum light chain (sLC), β 2 microglobulin (β 2 -MG), lactic dehydrogenase (LDH), and immunoglobulin (Ig) are routinely measured in the majority of Chinese hospitals. Imbalance of sLC ratio (involved light chain/uninvolved light chain) is frequently observed in MM patients. This study aimed to evaluate the screening value of sLC ratio, β 2 -MG, LDH, and Ig in MM patients using receiver operating characteristic (ROC) curves. Methods Data of 303 suspected MM patients, who were admitted to the Taizhou Central Hospital between March 2015 and July 2021, were retrospectively analyzed. In total, 69 patients (MM arm) met the International Myeloma Working Group (IMWG) updated criteria for the diagnosis of MM, while 234 patients were non-MM (non-MM arm). All patients’ sLC, β 2 -MG, LDH, and Ig were measured using commercially available kits according to the manufacturer’s instructions. The ROC curve analysis was employed to assess the screening value of sLC ratio, β 2 -MG, LDH, creatinine (Cr) and Ig. The statistical analysis was carried out by SPSS 26.0 (IBM, Armonk, NY, USA) and MedCalc 19.0.4 (Ostend, Belgium) software. Results There was no significant difference between the MM and non-MM arms in terms of gender, age and Cr. The median sLC ratio in the MM arm was 11.5333, which was significantly higher than that of 1.9293 in the non-MM arm ( P <0.001). The area under the curve (AUC) of sLC ratio was 0.875, which indicated a robust screening value. The optimal sensitivity and specificity were 81.16% and 94.87% respectively, when the sLC ratio was set as 3.2121. The serum levels of β 2 -MG and Ig were higher in the MM arm than those in the non-MM arm ( P <0.001). The AUC values of β 2 -MG, LDH, and Ig were 0.843 ( P <0.001), 0.547 ( P = 0 . 2627 ), and 0.723 ( P <0.001), respectively. The optimal cutoff values of β 2 -MG, LDH, and Ig were 1.95 mg/L, 220 U/L, and 46.4 g/L respectively, in the context of screening value. The triple combination of sLC ratio (3.2121), β 2 -MG (1.95 mg/L), and Ig (46.4 g/L) yielded a higher screening value compared with that of sLC ratio alone (AUC, 0.952; P <0.0001). The triple combination had a sensitivity of 94.20% and a specificity of 86.75%. The addition of LDH to the triple combination and formation of quadruple combination did not optimize the screening value, with AUC, sensitivity, and specificity of 0.952, 94.20%, and 85.47%, respectively. Conclusion The triple combination strategy (sLC ratio, 3.2121; β 2 -MG, 1.95 mg/L; Ig, 46.4 g/L) is accompanied by remarkable sensitivity and specificity for screening MM in Chinese hospitals.

The papillary thyroid carcinoma (PTC) metastasizes through lymphatic spread, but the follicular thyroid cancer (FTC) metastasis occurs by following hematogenous spread. To date, the molecular mechanism underlying different metastatic routes between PTC and FTC is still unclear. Here, we showed that specifically androgen-regulated gene (SARG) was significantly up-regulated in PTC, while obviously down-regulated in FTC through analyzing the Gene Expression Omnibus (GEO) database. Immunohistochemistry assay verified that the PTC lymph node metastasis was associated with higher levels of SARG protein in clinical PTC patient samples. SARG-knockdown decreased TPC-1 and CGTH-W3 cells viability and migration significantly. On the contrary, SARG-overexpressed PTC cells possessed more aggressive migratory ability and viability. In vivo, SARG overexpression dramatically promoted popliteal lymph node metastasis of xenografts from TPC-1 cells mouse footpad transplanting. Mechanistically, SARG overexpression and knockdown significantly increased and decreased the expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor 3 (VEGFR-3), respectively, thereby facilitating or inhibiting the tube formation in HUVECs. The tube formation experiment showed that SARG overexpression and knockdown promoted or inhibited the number of tube formations in HUVEC cells, respectively. Taken together, we showed for the first time the differential expression profile of SARG between PTC and FTC, and SARG promotes PTC lymphatic metastasis via VEGF-C/VEGFR-3 signal. It indicates that SARG may represent a target for clinical intervention in lymphatic metastasis of PTC.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

Abstract Essential thrombocythaemia (ET) and Waldenström macroglobulinaemia (WM) are two distinct disorders. Studies have reported several cases of myeloproliferative neoplasms (MPNs) with concomitant plasma cell dyscrasia. However, there were no reported cases of ET with concomitant WM to date. Here, we present a 55-year-old Chinese man with thrombocytosis and raised immunoglobulin level. Further investigations led to a diagnosis of ET and coexistent WM. Next-generation sequencing (NGS) of his bone marrow identified 3 mutated genes: JAK2 V617F, MYD88 L265P, and ATM F1036L. After being treated with pegylated interferon and low-dose aspirin, his platelet count normalized and immunoglobulin M (IgM) level reduced. To the best of our knowledge, this is the first reported case of dual pathology ET with WM.

Primary hepatic lymphoma (PHL) is an uncommon lymphoid tumor with varied clinical features and treatment outcome. In the present study, the case of a 56-year-old patient with PHL and no clinical presentation was reported. During a routine physical examination, multiple hypodense nodules were incidentally detected in right lobes of the liver and hepatic portal in an abdominal computed tomography scan. A liver biopsy revealed the presence of a non-Hodgkin's lymphoma diffuse large B cell type that was CD20-positive, followed by the diagnosis of a PHL. The patient was treated with R-CHOP, radiotherapy and R-Hyper-CVAD/R-HD MTX-ara-C, and complete remission was achieved.