Inflammatory disorders associated with trisomy 8‐myelodysplastic syndromes: French retrospective case‐control study

Wesner, N.; Drevon, Louis; Guédon, A.; Fraison, Jean Baptiste; Trad, S.; Kahn, Jean‐Emmanuel; Aouba, Achille; Gillard, J.; Ponsoye, Matthieu; Hanslik, Thomas; Gourguechon, C.; Liozon, É.; Laribi, Kamel; Rossignol, Julien; Hermine, Olivier; Adès, Lionel; Carrat, Fabrice; Fenaux, Pierre; Mékinian, A.; Fain, Olivier; Gfm, Minhemon

doi:10.1111/ejh.13174

Cited by 20 publications

(18 citation statements)

References 10 publications

(11 reference statements)

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“…The inflammatory molecules causing constitutive activation of TLR-signalling and subsequent downstream mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) activation have been implicated in the pathogenesis of MDS [166][167][168][169][170][171]. Notably, systematic inflammatory and autoimmune manifestations are also commonly (up to 25%) reported in MDS patients [172][173][174]. Notably, proinflammatory signalling, initiated by TGFβ1 within the BM microenvironment, triggers the molecular alterations and functional inhibition of MSC, which eventually contributes to ineffective haematopoiesis [175].…”

Section: Bmme Inflammation: a Friend Or A Foementioning

confidence: 99%

Nature or Nurture? Role of the Bone Marrow Microenvironment in the Genesis and Maintenance of Myelodysplastic Syndromes

Mian

Bonnet

2021

Cancers

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Myelodysplastic syndrome (MDS) are clonal haematopoietic stem cell (HSC) disorders driven by a complex combination(s) of changes within the genome that result in heterogeneity in both clinical phenotype and disease outcomes. MDS is among the most common of the haematological cancers and its incidence markedly increases with age. Currently available treatments have limited success, with <5% of patients undergoing allogeneic HSC transplantation, a procedure that offers the only possible cure. Critical contributions of the bone marrow microenvironment to the MDS have recently been investigated. Although the better understanding of the underlying biology, particularly genetics of haematopoietic stem cells, has led to better disease and risk classification; however, the role that the bone marrow microenvironment plays in the development of MDS remains largely unclear. This review provides a comprehensive overview of the latest developments in understanding the aetiology of MDS, particularly focussing on understanding how HSCs and the surrounding immune/non-immune bone marrow niche interacts together.

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Section: Bmme Inflammation: a Friend Or A Foementioning

confidence: 99%

Nature or Nurture? Role of the Bone Marrow Microenvironment in the Genesis and Maintenance of Myelodysplastic Syndromes

Mian

Bonnet

2021

Cancers

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“…Other clinical manifestations of Behçet's disease, such as arthritis or neutrophilic dermatosis, have also been described in MDS patients with trisomy 8, with the exception of ocular and neurologic manifestations that are usually absent. Other inflammatory manifestations associated with MDS with trisomy 8 have been reported less frequently: pyoderma gangrenosum (PG) [56], sweet syndrome (SS) [57], pulmonary alveolar proteinosis [58] and inflammatory arthritis [59]. Moreover, Zhao et al reported a higher incidence of TET2/IDH and SRSF2 mutations in a cohort of MDS/CMML patients with SIADs compared to MDS/CMML patients without, and identified that TET2/IDH and not SRSF2 mutations deeply modified the Treg and CD8+ T-cell subsets distribution [60].…”

Section: Characteristics Of the Underlying Mdsmentioning

confidence: 99%

Inflammatory and Immune Disorders Associated with Myelodysplastic Syndromes

Jachiet

Fenaux

Sevoyan

et al. 2021

Hemato

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Systemic auto-inflammatory or autoimmune diseases (SIADs) develop in up to a quarter of patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). With or without the occurrence of SIADs, the distribution of MDS subtypes and the international or CMML-specific prognostic scoring systems have been similar between MDS/CMML patients. Moreover, various SIADs have been described in association with MDS, ranging from limited clinical manifestations to systemic diseases affecting multiple organs. Defined clinical entities including systemic vasculitis, connective tissue diseases, inflammatory arthritis and neutrophilic diseases are frequently reported; however, unclassified or isolated organ impairment can also be seen. Although the presence of SIADs does not impact the overall survival nor disease progression to acute myeloid leukemia, they can help with avoiding steroid dependence and make associated adverse events of immunosuppressive drugs challenging. While therapies using steroids and immunosuppressive treatment remain the backbone of first-line treatment, increasing evidence suggests that MDS specific therapy (hypomethylating agents) and sparing steroids may be effective in treating such complications based on their immunomodulatory effect. The aim of this review was to analyze the epidemiological, pathophysiological, clinical and therapeutic factors of systemic inflammatory and immune disorders associated with MDS.

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“…All three harbored a trisomy 8 in their bone marrow (Table 1). The association between trisomy 8 and Behcet's‐like phenotype was first reported in 1996 by Yano et al., 31 and since then was reported in a few small series, 12–15 mainly in patients from East Asian ethnicity. Interestingly, an increased incidence of Behcet's disease is reported also in patients with constitutional trisomy 8, 32 but the pathological cause of the specific phenotype is still not known 14 .…”

Section: Discussionmentioning

confidence: 94%

Pediatric myelodysplastic syndrome with inflammatory manifestations: Diagnosis, genetics, treatment, and outcome

Yanir

Krauss

Stein

et al. 2021

Pediatric Blood & Cancer

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Background Inflammatory manifestations (IM) are well described in adult patients with myelodysplastic syndrome (MDS), but the presentation is highly variable and no standardized treatment exists. This phenomenon is rarely reported in children. As more pediatric patients are hematopoietic stem cell transplantation (HSCT) candidates, the role of anti‐inflammatory treatment in relation to HSCT should be defined. Procedure Here, we report a series of five children from a tertiary center. We describe the clinical presentation, molecular findings, and treatment options. Results All patients presented with advanced MDS with blast percentages ranging 10–30%, all had severe IM. One patient had MDS secondary to severe congenital neutropenia, the other four patients had presumably primary MDS. All four were found to harbor a PTPN11 gene driver mutation, which is found in 35% of cases of juvenile myelomonocytic leukemia (JMML). The mutation was present in the myeloid lineage but not in T lymphocytes. Three had symptoms of Behcet's‐like disease with trisomy 8 in their bone marrow. All patients were treated with anti‐inflammatory medications (mainly systemic steroids) in an attempt to bring them to allogeneic HSCT in a better clinical condition. All demonstrated clinical improvement as well as regression in their MDS status post anti‐inflammatory treatment. All have recovered from both MDS and their inflammatory symptoms post HSCT. Conclusion Primary pediatric MDS with IM is driven in some cases by PTPN11 mutations, and might be on the clinical spectrum of JMML. Anti‐inflammatory treatment may reverse MDS progression and improve the outcome of subsequent HSCT.

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Inflammatory disorders associated with trisomy 8‐myelodysplastic syndromes: French retrospective case‐control study

Abstract: The spectrum of IADs associated with trisomy 8-positive MDS/MPN is dominated by Behçet's-like disease. Steroid therapy is effective, but mostly sparing therapies are necessary. Azacytidine could be an effective alternative.

Cited by 20 publications

References 10 publications

Nature or Nurture? Role of the Bone Marrow Microenvironment in the Genesis and Maintenance of Myelodysplastic Syndromes

Nature or Nurture? Role of the Bone Marrow Microenvironment in the Genesis and Maintenance of Myelodysplastic Syndromes

Inflammatory and Immune Disorders Associated with Myelodysplastic Syndromes

Pediatric myelodysplastic syndrome with inflammatory manifestations: Diagnosis, genetics, treatment, and outcome

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