Prognostic value of bone marrow MUC4 expression in acute myeloid leukaemia

Abdelhady, Ahmed Kadry; Hamid, Fatma F. Abdel; Hassan, Noha; Ibrahim, Doaa

doi:10.1080/09674845.2020.1754583

Cited by 5 publications

(4 citation statements)

References 40 publications

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“…Thereof, mutations in the following genes were exclusively seen in LAIP2 (MFC ANXA2 hi ): CLIC6, DDX51, HTT, MUC4, PIEZO1, PRG4, PTPRZ1. Here, previous studies found mastermind like 2 (MAML2) to be a rare fusion partner of KMT2A in patients with myelodysplastic syndromes and secondary AML as well as acute lymphoblastic leukemia (ALL); mucin 4 (MUC4) expression to be associated with adverse prognosis in AML and piezo type mechanosensitive ion channel component 1 (PIEZO1) frequently mutated in patients with hereditary xerocytosis, hereditary stomatocytosis, respectively (16)(17)(18). Although mutational profiling demonstrated high intra-tumor heterogeneity and clonal architecture, genomic characterization could not provide a valid link to the severe coagulopathy with hyperfibrinolysis, coagulation in general, respectively.…”

Section: Resultsmentioning

confidence: 90%

Case Report: ANXA2 Associated Life-Threatening Coagulopathy With Hyperfibrinolysis in a Patient With Non-APL Acute Myeloid Leukemia

et al. 2021

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Patients with acute promyelocytic leukemia (APL) often present with potentially life-threatening hemorrhagic diathesis. The underlying pathomechanisms of APL-associated coagulopathy are complex. However, two pathways considered to be APL-specific had been identified: 1) annexin A2 (ANXA2)-associated hyperfibrinolysis and 2) podoplanin (PDPN)-mediated platelet activation and aggregation. In contrast, since disseminated intravascular coagulation (DIC) is far less frequent in patients with non-APL acute myeloid leukemia (AML), the pathophysiology of AML-associated hemorrhagic disorders is not well understood. Furthermore, the potential threat of coagulopathy in non-APL AML patients may be underestimated. Herein, we report a patient with non-APL AML presenting with severe coagulopathy with hyperfibrinolysis. Since his clinical course resembled a prototypical APL-associated hemorrhagic disorder, we hypothesized pathophysiological similarities. Performing multiparametric flow cytometry (MFC) and immunofluorescence imaging (IF) studies, we found the patient’s bone-marrow mononuclear cells (BM-MNC) to express ANXA2 - a biomarker previously thought to be APL-specific. In addition, whole-exome sequencing (WES) on sorted BM-MNC (leukemia-associated immunophenotype (LAIP)1: ANXAlo, LAIP2: ANXAhi) demonstrated high intra-tumor heterogeneity. Since ANXA2 regulation is not well understood, further research to determine the coagulopathy-initiating events in AML and APL is indicated. Moreover, ANXA2 and PDPN MFC assessment as a tool to determine the risk of life-threatening DIC in AML and APL patients should be evaluated.

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Section: Resultsmentioning

confidence: 90%

Case Report: ANXA2 Associated Life-Threatening Coagulopathy With Hyperfibrinolysis in a Patient With Non-APL Acute Myeloid Leukemia

et al. 2021

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“…MUC4 expression is dysregulated in colon adenocarcinoma, [128] reports of upregulation were also found for breast, [129,130] lungs, [131] ovarian, [132] pancreas [133,134] cancer, and acute myeloid leukemia. [135] There are few examples, such as mucoepidermoid carcinomas of the salivary gland, where overexpression correlates with a better prognosis. [136,137] However, in most scenarios, overexpression correlates with poor clinical outcomes, and MUC 4 expression level can be used as a prognostic marker.…”

Section: The Mucin Muc4mentioning

confidence: 99%

The Development of Vaccines from Synthetic Tumor‐Associated Mucin Glycopeptides and their Glycosylation‐Dependent Immune Response

Stergiou

Urschbach

Gabba

et al. 2021

The Chemical Record

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Tumor-associated carbohydrate antigens are overexpressed as altered-self in most common epithelial cancers. Their glycosylation patterns differ from those of healthy cells, functioning as an ID for cancer cells. Scientists have been developing anti-cancer vaccines based on mucin glycopeptides, yet the interplay of delivery system, adjuvant and tumor associated MUC epitopes in the induced immune response is not well understood. The current state of the art suggests that the identity, abundancy and location of the glycans on the MUC backbone are all key parameters in the cellular and humoral response. This review shares lessons learned by us in over two decades of research in glycopeptide vaccines. By bridging synthetic chemistry and immunology, we discuss efforts in designing synthetic MUC1/4/16 vaccines and focus on the role of glycosylation patterns. We provide a brief introduction into the mechanisms of the immune system and aim to promote the development of cancer subunit vaccines.

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“…Abelhardy et al [69] in this issue of the journal consider the prognostic value of bone marrow MUC4 expression in acute myeloid leukaemia (AML), an aggressive haematological malignancy affecting adults and linked to a combination of environmental factors, chromosomal aberrations, and gene mutations. It is a cytogenetically, and molecularly heterogeneous disease characterized by over-proliferation and accumulation of myeloid blasts in the bone marrow and blood [70,71].…”

Section: Biomarkersmentioning

confidence: 99%

British Journal of Biomedical Science in 2020. What have we learned?

Brown

Orchard

Rhodes

2020

British Journal of Biomedical Science

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Each year the British Journal of Biomedical Science publishes a 'What have we learned' editorial designed to introduce readers within the major disciplines of laboratory medicine to developments outside their immediate area. In addition it is designed to inform a wider readership of the advances in the diagnosis and treatment of disease. To this end, in 2020 the journal published 39 articles covering the disciplines within Biomedical Science in the 4 issues comprising volume 77. These included a review of COVID-19 in this issue, 27 original articles, 6 Biomedical Science 'In Brief' and 4 case histories. 27 of the articles involved molecular techniques, with one of these comparing results with a mass spectrometry based method. The preponderance of molecular genetic studies gives us a good idea of the likely future direction of the disciplines

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Prognostic value of bone marrow MUC4 expression in acute myeloid leukaemia

Cited by 5 publications

References 40 publications

Case Report: ANXA2 Associated Life-Threatening Coagulopathy With Hyperfibrinolysis in a Patient With Non-APL Acute Myeloid Leukemia

Case Report: ANXA2 Associated Life-Threatening Coagulopathy With Hyperfibrinolysis in a Patient With Non-APL Acute Myeloid Leukemia

The Development of Vaccines from Synthetic Tumor‐Associated Mucin Glycopeptides and their Glycosylation‐Dependent Immune Response

British Journal of Biomedical Science in 2020. What have we learned?

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