7042 Background: AML1-MTG16 and FUS-ERG are two rare fusion genes in acute myeloid leukemia (AML). Their clinical characteristics and factors influencing prognosis have been summarized in a cohort of pediatric patients, but no systematic review is approached in adult. Methods: We retrospectively analyzed the clinical data of adult AML patients with AML1-MTG16 or FUS-ERG fusion genes, who were reported on Mitelman Database, PubMed and China national knowledge infrastructure (CNKI) from 1988 to 2022 or have received treatment in the First Affiliated Hospital, Zhejiang University School of Medical, and compared them with patients with RUNX1-RUNX1T1, exploring their clinical features and prognosis. Results: 314 patients were totally included for analysis. In comparison of RUNX1-RUNX1T1 group (n = 209), FUS-ERG-positive patients (n = 108) significantly exhibited a younger onset age (34.5y vs. 41y), higher WBC count (16.7 ×10 9 /L vs. 10.4×10 9 /L), higher recurrence rate (61.8% vs. 30.4%), and a worse response to chemotherapy (complete remission rate: 71.6% vs. 91.8%), while patients with AML1-MTG16 (n = 24) presented primarily as the secondary AML (83.3%) with a significantly elder age (56y vs. 41y). The FUS-ERG patients had a worse median overall survival (OS) of 13 months (95%CI: 11.6-14.4, P < 0.01) and a worse median disease free survival (DFS) of 7.5 months (95%CI: 6.5-8.5, P < 0.05) than control group, which also occurred in those had AML1-MTG16 gene with a median OS of 18.5 months (95%CI: 12.4-24.6, P < 0.01) and a median DFS of 14 months (95%CI: 3.7-24.3, P = 0.10). As shown in the table below, CR after induction chemotherapy, hematopoietic stem cell transplantation (HSCT), trisomy, monosomy and age of patients were associated with the prognosis of FUS-ERG group. Unlike pediatric patients, the adult AML1-MTG16 patients did not perform a better outcome (OS: HR = 0.90, P = 0.83; DFS: HR = 0.54, P = 0.34) in contrast with FUS-ERG patients. Conclusions: The retrospective study summarized the clinical characteristics of AML1-MTG16 and FUS-ERG, identifying their distinctions on multiple aspects such as prior disease, recurrence rate, response to chemotherapy and cytogenetics. AML1-MTG16 exhibited extremely bad prognosis like FUS-ERG in adult population, which varied from the results in pediatric cohort. Several factors including age, CR after induction chemotherapy, HSCT, trisomy and monosomy were relevant to the prognosis of FUS-ERG. [Table: see text]
Summary Large amounts of azurophilic granules are considered to be a morphological feature of acute promyelocytic leukaemia (APL). However, a small percentage of acute myeloid leukaemia (AML) patients also have a large number of azurophilic granules. A large cohort of 3210 AML patients in our hospital was screened to identify AML patients who had a large number of azurophilic granules. The clinical parameters of these patients were collected and compared with typical AML patients (control Group 1) and APL patients (control Group 2). The incidence of AML with a large number of azurophilic granules was 1.26%. The fibrinogen and D‐dimer levels of patients in the study group were more similar to those of patients in control Group 2, as was the incidence of bleeding events. Additionally, patients in the study group had higher FLT3‐ITD and NPM1 mutation rates than patients in control Group 1. Finally, patients in the study group had a higher 30‐day mortality rate than those in control Group 2 (24.2% vs. 9.09%) and showed a higher 30‐day mortality trend than those in control Group 1. Therefore, we should pay more attention to the prevention of coagulation dysfunction and bleeding events for these patients.
Genetic heterogeneity poses a great challenge to the understanding and management of acute myeloid leukemia (AML). Knowledge of the IKZF1 mutation in AML specifically is extremely limited. In a previous work, we described the distribution pattern of IKZF1 mutation in AML, but its clinical impact has remained undefined due to the limited number of cases. Herein, we attempt to answer this question in one relatively large cohort covering 522 newly diagnosed AML patients. A total of 26 IKZF1 mutations were found in 20 AML patients (20/522, 3.83%). This condition has a young median age of onset of morbidity (P = 0.032). The baseline characteristics of IKZF1-mutated and wild-type patients were comparable. IKZF1 mutation showed significant co-occurrences with CEBPA (P < 0.001), SF3B1 (P < 0.001), and CSF3R (P = 0.005) mutations, and it was mutually exclusive with NPM1 mutation (P = 0.033). Although IKZF1-mutated AML was more preferably classified into the intermediate-risk group (P = 0.004), it showed one inferior complete remission rate (P = 0.032). AML with high burden of IKZF1 mutation (variant allele frequency > 0.20) showed relatively short overall survival period (P = 0.012), and it was an independent factor for the increased risk of death (hazard ratio, 6.101; 95% CI 2.278-16.335; P = 0.0003). In subgroup analysis, our results showed that IKZF1 mutation conferred poor therapeutic response and prognosis for SF3B1-mutated AML (P = 0.0017). We believe this work improves our knowledge of IKZF1 mutation.
Background: Somatic mutations involving epigenetic regulators, histone modification and chromatin regulation, splicing components, transcription factors and signaling regulator genes are common in chronic myelomonocytic leukemia (CMML) patients. It has been consensus that ASXL1 mutations have adversely impact on overall survival (OS), while the effect of TET2 mutations remains controversial and undefined. Methods: ASXL1 and TET2 mutations were analyzed in 141 patients with CMML using Sanger sequencing, with the aim to identify the interplay of ASXL1 and TET2 mutations in the prognosis of CMML. Results: Sixty-five (46.1%) of the CMML patients harbored ASXL1 mutations (frameshift and nonsense), and 46 (32.6%) had TET2 mutations (frame shift, nonsense and missense). In a separate multivariable analysis that included the Mayo Prognostic Model as a single variable along with ASXL1wt/TET2wt, the respective hazard ratios of ASXL1mut/TET2mut, ASXL1mut/TET2wt and ASXL1wt/TET2mut were 4.7 (95% CI, 2.2–10.3; P<0.001), 2.2 (95% CI, 1.1–4.2; P=0.025) and 1.3 (95% CI, 0.6–2.5; P=0.521). Conclusions: Our study showed that ASXL1 mutations predict inferior OS, and additional TET2 mutations were associated with poor survival in the presence of ASXL1 mutations of CMML patients.
Abstract Huntingtin interacting protein 1 (HIP1) is an endocytic protein which is overexpressed in a variety of human cancers and involved in cancer-causing translocation in leukemia. However, the prognostic impact of HIP1 expression on AML remains unclear. In this study, quantification of HIP1 transcript by real-time quantitative PCR in bone marrow blasts was performed in 270 AML patients. As a result, high HIP1 expression was seen more frequently in older patients, M4/M5 morphology and genes of NPM1 and DNMT3A mutations, and underrepresented in favorable karyotype subgroups and CEBPA double allele mutations in our AML patients. We also found high HIP1 expressers showed lower levels of hemoglobin. In addition, overexpression of HIP1 was associated with an inferior overall survival. The prognostic value of HIP1 expression was validated in patients from an independent TCGA cohort. Notably, up-regulation of miR-16, miR-15a, miR-28 and miR-660 were seen in high HIP1 expressers from the two independent cohorts. In vitro , interfereing of HIP1 expression by siRNA suppressed the proliferation of leukemic cells, and downregulation of these miRNAs were seen in THP-1 and Kasumi cell lines after silencing HIP1 expression. In conclusion, the HIP1 gene expression might serve as a reliable predictor for overall survival in AML patients.
Abstract In hematologic malignancies (HM) patients, COVID-19 infections carry a significant risk of mortality due to disease status, treatment, and other factors.The risk factors of the severity and persistence of COVID-19 infections remains unclear. A study observed adults with HM diagnosed with COVID-19 from November 2022 to February 2023. Patient blood samples yielded biochemical data, with COVID-19 confirmed via RNA or antigen testing. In the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Using advanced multivariate logistic regression, high C-reactive protein levels (≥100mg/L) significantly increased the risk of severe/critical conditions in HM patients with COVID-19 (OR: 3.415, 95% CI: 1.294-9.012; p=0.013). Patients enduring Omicron infection beyond 30 days were deemed persistent, in contrast to those achieving infection control within this duration. The research indicated that taking ＜2 vaccine doses (OR: 0.202, 95% CI: 0.048-0.857; p=0.030), having low IgG levels (＜1000 mg/dl) (OR: 0.129, 95% CI: 0.027-0.607; p=0.010), and increased interleukin-6 levels (≥12pg/ml) (OR: 5.098, 95% CI: 1.118-23.243; p=0.035) were key indicators of ongoing infection. A significant difference in survival rates was observed between patients with persistent and non-persistent infections, with the latter showing better survival outcomes (P<0.001). In conclusion, increased C-reactive protein levels had a higher likelihood of severe health outcomes for HM patients with COVID-19 infection. Persistent infections tended to be more prevalent in those with lower vaccine dosages, diminished IgG levels, and escalated interleukin-6 levels.
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