Figure - available from: Annals of Hematology
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Bone marrow cell morphology of case 3. a, b MDS RAEB. Both images suggest granulocytic dysplasia. a mainly shows the decrease of cytoplasmic particles, and b mainly reflects the imbalance of nucleoplasmic development. c, d MDS progresses to leukemia. Both images suggest an increase in blasts
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To investigate the pathogenesis and the refractory/relapse mechanisms in patients with t(16;21)(p11;q22), we retrospectively analyzed the clinical data of six cases in our hospital and sixty-two cases reported in the literature. Among the patients in our hospital, five cases were diagnosed as acute leukemia, and one was myelodysplastic syndrome evo...
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... In acute myeloid leukemia (AML), a small subset of patients have t(16:21) ERG:FUS fusion, which was first identified in 1994 as a driver of leukemogenesis [5]. A recent review of 52 patients with ERG:FUS demonstrated poor prognosis as well as association with GATA2, SMAD4, and RUNX1 mutation [6]. The 2022 WHO classification recognizes ERG as an important driver in acute erythroid leukemia [7]. ...
Introduction: The erythroblastosis transformation-specific regulated gene 1 (ERG) is a transcription factor that can be used as an immunohistochemical (IHC) marker in the diagnosis and prognostication of malignancy. ERG was initially used in prostate cancer; however, it is a useful marker in extramedullary myeloid disease. Patients with acute myeloid leukemia (AML), dry bone marrow aspirate, and CD34, CD117-negative blast cells can be in a diagnostic dilemma. This audit aimed to (a) validate ERG IHC in bone marrow trephine samples, (b) quantify ERG IHC positivity in an AML cohort, and correlate concordance with CD34 and CD117 IHC, when available, and (c) to see whether ERG is a useful adjunct in the diagnosis of cases of AML.
Methods: A retrospective audit was completed of all new and relapsed cases of AML over one year at a single center. For inclusion, patients needed a trephine specimen at presentation, and all had a hematoxylin and eosin(H&E) specimen, ERG IHC, and at least one or both of CD34 and CD117 IHC. Four pathologists independently assessed the stains quantitatively and qualitatively in comparison to the morphology seen on the H&E sample. The kappa value was used to assess agreement.
Results: Seventeen patients with AML met the inclusion criteria. All specimens had H&E, CD34, and ERG stains; 9/17 (53%) had CD117 IHC. ERG demonstrated high concordance with blast cells on H&E morphology, with a high agreement among pathologists. Qualitatively, pathologists recognized that ERG spared lymphoid nodules; however, it also stained granulocytes at various maturation stages.
Conclusion: ERG is a sensitive marker for the diagnosis of AML. ERG can help visualize blast cells that have been confirmed by ancillary tests. More research into the utility of ERG in AML diagnostics is recommended.
... On the other hand, we noticed that all cases positive for CBFA2T3::GLIS2 and FUS::ERG were concentrated in Cluster 4 ( Figure 1), both of which have been reported to exhibit a dismal prognosis. [12][13][14][15][16] Nevertheless, cases in Cluster 4 without these two fusions had a dismal prognosis as well ( Figure 2C). We further analysed the difference in prognosis of cases with the same FAB classification distributed into different clusters ( Figure 2D-G). ...
Acute myeloid leukaemia (AML) is a highly heterogeneous disease, exhibiting diverse subtypes according to the characteristics of tumour cells. The immunophenotype is one of the aspects acquired routinely through flow cytometry in the diagnosis of AML. Here, we characterized the antigen expression in paediatric AML cases across both morphological and molecular genetic subgroups. We discovered a subgroup of patients with unfavourable prognosis that can be immunologically characterized, irrespective of morphological FAB results or genetic aberrations. Cox regression analysis unveiled key antigens influencing the prognosis of AML patients. In terms of underlying genotypes, we observed that the antigenic profiles and outcomes of one specific group, primarily composed of CBFA2T3::GLIS2 and FUS::ERG, were analogous to the reported RAM phenotype. Overall, our data highlight the significance of immunophenotype to tailor treatment for paediatric AML.
... The risk of AML evolution for a particular MDS is calculated taking into consideration clinical and genetic variables 10 . Hence, two large groups of MDS patients-low and high-risk, can be differentiated in terms of their clinical evolution 11 . ...
A dataset comprising metagenomes of outpatients (n = 28) with acute leukemia (AL) and healthy controls (n = 14) was analysed to investigate the associations between gut microbiota composition and metabolic activity and AL. According to the results obtained, no significant differences in the microbial diversity between AL outpatients and healthy controls were found. However, significant differences in the abundance of specific microbial clades of healthy controls and AL outpatients were found. We found some differences at taxa level. The relative abundance of Enterobacteriaceae, Prevotellaceae and Rikenellaceae was increased in AL outpatients, while Bacteirodaceae, Bifidobacteriaceae and Lachnospiraceae was decreased. Interestingly, the abundances of several taxa including Bacteroides and Faecalibacterium species showed variations based on recovery time from the last cycle of chemotherapy. Functional annotation of metagenome-assembled genomes (MAGs) revealed the presence of functional domains corresponding to therapeutic enzymes including l-asparaginase in a wide range of genera including Prevotella, Ruminococcus, Faecalibacterium, Alistipes, Akkermansia. Metabolic network modelling revealed potential symbiotic relationships between Veillonella parvula and Levyella massiliensis and several species found in the microbiota of AL outpatients. These results may contribute to develop strategies for the recovery of microbiota composition profiles in the treatment of patients with AL.
... Pathogenicity predictors for TFs implicated in predisposition to BMF and HM. Comparison of pathogenicity predictor score for known predisposition TFs and potential TF genes isolated from Table 1 hematological malignant fusions (ERG/TMPRSS2, ERG-EWS, FEV-EWS) (i.e., prostate cancer) as well as hematological malignant fusions (e.g., TLS/FUS-ERG and FLI1-EWS seen in myeloid leukemia and Ewing's Sarcoma, respectively) (93). Germline ETV6 pathogenic variants phenocopy RUNX1 germline pathogenic variants in terms of platelet defects, heightened HM predisposition and their association with a poorer overall survival but, unlike RUNX1, clonal hematopoiesis has not been reported in ETV6 carriers (94,95). ...
Transcription factors (TFs) play a critical role as key mediators of a multitude of developmental pathways, with highly regulated and tightly organized networks crucial for determining both the timing and pattern of tissue development. TFs can act as master regulators of both primitive and definitive hematopoiesis, tightly controlling the behavior of hematopoietic stem and progenitor cells (HSPCs). These networks control the functional regulation of HSPCs including self-renewal, proliferation, and differentiation dynamics, which are essential to normal hematopoiesis. Defining the key players and dynamics of these hematopoietic transcriptional networks is essential to understanding both normal hematopoiesis and how genetic aberrations in TFs and their networks can predispose to hematopoietic disease including bone marrow failure (BMF) and hematological malignancy (HM). Despite their multifaceted and complex involvement in hematological development, advances in genetic screening along with elegant multi-omics and model system studies are shedding light on how hematopoietic TFs interact and network to achieve normal cell fates and their role in disease etiology. This review focuses on TFs which predispose to BMF and HM, identifies potential novel candidate predisposing TF genes, and examines putative biological mechanisms leading to these phenotypes. A better understanding of the genetics and molecular biology of hematopoietic TFs, as well as identifying novel genes and genetic variants predisposing to BMF and HM, will accelerate the development of preventative strategies, improve clinical management and counseling, and help define targeted treatments for these diseases.
