Pediatric Myelodysplastic Syndromes

Glaubach, Taly; Robinson, Lisa J.; Corey, Seth J.

doi:10.1097/mph.0000000000000046

Cited by 36 publications

(48 citation statements)

References 11 publications

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“…Lack of differences in expression levels of Dicer1, Drosha and CXCL12 was further confirmed by RT-PCR (data not shown). This supports the current understanding that pediatric and adult MDS are two different diseases as previous studies have highlighted the differences between adult and pediatric MDS, e.g., in response to treatment and rarity and prognostic value of (epi-)genetic mutations in the hematopoietic compartment (Hasle et al, 2004;Glaubach et al, 2014;Hirabayashi et al, 2012). Besides IL-6, genes included in the clustered analysis did not encode for molecules known to be involved in MSC signaling as reviewed by Le Blanc and Mougiakakos (2012).…”

Section: Discussionsupporting

confidence: 80%

Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro

et al. 2015

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Pediatric myelodysplastic syndrome (MDS) is a heterogeneous disease covering a spectrum ranging from aplasia (RCC) to myeloproliferation (RAEB(t)). In adult-type MDS there is increasing evidence for abnormal function of the bone-marrow microenvironment. Here, we extensively studied the mesenchymal stromal cells (MSCs) derived from children with MDS. MSCs were expanded from the bone-marrow of 17 MDS patients (RCC: n=10 and advanced MDS: n=7) and pediatric controls (n=10). No differences were observed with respect to phenotype, differentiation capacity, immunomodulatory capacity or hematopoietic support. mRNA expression analysis by Deep-SAGE revealed increased IL-6 expression in RCC- and RAEB(t)-MDS. RCC-MDS MSC expressed increased levels of DKK3, a protein associated with decreased apoptosis. RAEB(t)-MDS revealed increased CRLF1 and decreased DAPK1 expressions. This pattern has been associated with transformation in hematopoietic malignancies. Genes reported to be differentially expressed in adult MDS-MSC did not differ between MSC of pediatric MDS and controls. An altered mRNA expression profile, associated with cell survival and malignant transformation, of MSC derived from children with MDS strengthens the hypothesis that the micro-environment is of importance in this disease. Our data support the understanding that pediatric and adult MDS are two different diseases. Further evaluation of the pathways involved might reveal additional therapy targets.

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Section: Discussionsupporting

confidence: 80%

Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro

et al. 2015

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“…For the 80–90% of MDS which is not therapy-related, there are several differences in disease characteristics between MDS occurring in the young compared to the elderly, suggesting distinct leukemogenic drivers in these age groups (Figure 1B)[18,19]. At the population level, first-degree relatives of the under 21 year-old patients with MDS and AML are at a significantly increased risk of AML/MDS (relative risk 6.5×) compared to the general population; in contrast, this familial aggregation is not seen for the MDS population as a whole, underscoring a significantly greater contribution of genetic factors to leukemogenesis in the young[20].…”

Section: Epidemiology Of Mdsmentioning

confidence: 99%

Genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia in children and young adults

Babushok

Bessler

Olson

2015

Leukemia & Lymphoma

104

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Myelodysplastic syndrome (MDS) is a clonal blood disorder characterized by ineffective hematopoiesis, cytopenias, dysplasia and an increased risk of acute myeloid leukemia (AML). With the growing availability of clinical genetic testing, there is an increasing appreciation that a number of genetic predisposition syndromes may underlie apparent de novo presentations of MDS/AML, particularly in children and young adults. Recent findings of clonal hematopoiesis in acquired aplastic anemia add another facet to our understanding of the mechanisms of MDS/AML predisposition. As more predisposition syndromes are recognized, it is becoming increasingly important for hematologists and oncologists to have familiarity with the common as well as emerging syndromes, and to have a systematic approach to diagnosis and screening of at risk patient populations. Here, we provide a practical algorithm for approaching a patient with a suspected MDS/AML predisposition, and provide an in-depth review of the established and emerging familial MDS/AML syndromes caused by mutations in the ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1, SRP72 genes. Finally, we discuss recent data on the role of somatic mutations in malignant transformation in acquired aplastic anemia, and review the practical aspects of MDS/AML management in patients and families with predisposition syndromes.

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“…It is well known that after years of BM insufficiency with a more or less pronounced deficit in all three cell series, patients pass into a phase of insidiously increasing blast counts [9]. Morphological evaluations of peripheral blood and of bone marrow are important components in the evaluation of pediatric myelodysplasia [10]. In our case, bone marrow showed no signs of marrow failure, but the BMB indicated myelofibrosis, with dysplasia, and a blast count of 10%.…”

Section: Discussionmentioning

confidence: 79%

Myelodysplastic syndrome with myelofibrosis in a 12-year-old patient – A case report

Oltean

Chinceşan

Mărginean

et al. 2018

Revista Romana De Medicina De Laborator

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Pediatric Myelodysplastic Syndromes

Cited by 36 publications

References 11 publications

Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro

Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro

Genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia in children and young adults

Myelodysplastic syndrome with myelofibrosis in a 12-year-old patient – A case report

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