Aggressive CD8+ epidermotropic cutaneous T-cell lymphoma associated with homozygous mutation in SAMHD1

Merati, Miesha; Buethe, Douglas J.; Cooper, Kevin D.; Honda, Kazuo; Wang, Heng; Gerstenblith, Meg R.

doi:10.1016/j.jdcr.2015.05.003

Cited by 22 publications

(21 citation statements)

References 10 publications

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“…Several mechanisms of resistance development have been proposed, based on the deregulation of individual genes in relapsed AML, including SAMHD1 , EZH2 , and KDM6A . SAMHD1 encodes for a deoxynucleoside triphosphate triphosphohydrolase and is commonly mutated in T cell lymphomas, chronic lymphocytic leukemia, and colon cancer . Although SAMHD1 has been shown to sensitize cancer cells towards chemotherapy, it was reported that in AML, expression of SAMHD1 is inversely correlated to cytarabine response in vitro and in vivo .…”

Section: Molecular Mechanisms Of Chemotherapy Resistancementioning

confidence: 99%

“…SAMHD1 encodes for a deoxynucleoside triphosphate triphosphohydrolase and is commonly mutated in T cell lymphomas, chronic lymphocytic leukemia, and colon cancer. [48][49][50] Although SAMHD1 has been shown to sensitize cancer cells towards chemotherapy, 51 it was reported that in AML, expression of SAMHD1 is inversely correlated to cytarabine response in vitro and in vivo. 52 EZH2 encodes a histone methyltransferase and is commonly mutated at AML diagnosis and at relapse.…”

Section: Molecular Mechanisms Of Chemotherapy Resistancementioning

confidence: 99%

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Clonal evolution of acute myeloid leukemia from diagnosis to relapse

Vosberg

Greif

2019

Genes Chromosomes & Cancer

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Based on the individual genetic profile, acute myeloid leukemia (AML) patients are classified into clinically meaningful molecular subtypes. However, the mutational profile within these groups is highly heterogeneous and multiple AML subclones may exist in a single patient in parallel. Distinct alterations of single cells may be key factors in providing the fitness to survive in this highly competitive environment. Although the majority of AML patients initially respond to induction chemotherapy and achieve a complete remission, most patients will eventually relapse. These points toward an evolutionary process transforming treatment‐sensitive cells into treatment‐resistant cells. As described by Charles Darwin, evolution by natural selection is the selection of individuals that are optimally adapted to their environment, based on the random acquisition of heritable changes. By changing their mutational profile, AML cell populations are able to adapt to the new environment defined by chemotherapy treatment, ultimately leading to cell survival and regrowth. In this review, we will summarize the current knowledge about clonal evolution in AML, describe different models of clonal evolution, and provide the methodological background that allows the detection of clonal evolution in individual AML patients. During the last years, numerous studies have focused on delineating the molecular patterns that are associated with AML relapse, each focusing on a particular genetic subgroup of AML. Finally, we will review the results of these studies in the light of Darwinian evolution and discuss open questions regarding the molecular background of relapse development.

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Section: Molecular Mechanisms Of Chemotherapy Resistancementioning

confidence: 99%

Section: Molecular Mechanisms Of Chemotherapy Resistancementioning

confidence: 99%

Clonal evolution of acute myeloid leukemia from diagnosis to relapse

Vosberg

Greif

2019

Genes Chromosomes & Cancer

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“…Somatic mutations in SAMHD1 have also been identified in other hematopoietic and solid neoplasms [13, 17, 53–60]. A homozygous germline mutation in SAMHD1 was recently identified in a patient with an aggressive type of CTCL [61]. Finally, deletions in the SAMHD1 locus were also identified in 12% of SS patients, and novel mutations in SAMHD1 were identified in 3% of SS patients [19].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-181 contributes to downregulation of SAMHD1 expression in CD4+ T-cells derived from Sèzary syndrome patients

et al. 2017

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Sézary syndrome (SS) is a rare subtype of cutaneous T-cell lymphoma (CTCL) that is characterized by aggressive spread of neoplastic CD4+ T-cells from the skin into the bloodstream with metastasis to visceral organs. The deoxynucleoside triphosphohydrolase SAMHD1 is highly expressed in normal CD4+ T-cells, while its expression is down-regulated in CD4+ T-cells from SS patients. MicroRNA (miR) dysregulation is an important epigenetic mechanism in the pathogenesis and progression of SS. MiR-181 has been shown to inhibit SAMHD1 expression in cell lines and was identified as an important prognostic biomarker in CTCL. However, whether SAMHD1 is down-regulated by miR-181 in primary CD4+ T-cells of SS patients is unknown. Compared to normal CD4+ T-cells, SAMHD1 protein expression is significantly reduced in transformed CD4+ T-cell lines and CD4+ T-cells from SS patients, which inversely correlates with increased miR-181 levels in these cells. Over-expression of miR-181b in primary CD4+ T-cells from healthy donors significantly decreased SAMHD1 protein level, but not mRNA level. In contrast, inhibition of miR-181 in a CD4+ T-cell line significantly increased the level of SAMHD1 protein expression. Our results demonstrate that miR-181 is an important regulator of SAMHD1 protein expression in neoplastic CD4+ T-cells, likely through a mechanism of translational inhibition.

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“…Additionally, SAMHD1 is mutated in chronic lymphocytic leukemia and involved in response to DNA damage, implicating that SAMHD1 plays a tumor‐suppressor role in chronic lymphocytic leukemia . Moreover, SAMHD1 mutation was found in colon cancer and epidermotropic cutaneous T cell lymphoma . Together, these discoveries give evidence that SAMHD1 regulation can be associated with cancers.…”

Section: Cancer‐associated Samhd1 Functionmentioning

confidence: 92%

“…124,125 Moreover, SAMHD1 mutation was found in colon cancer and epidermotropic cutaneous T cell lymphoma. 126,127 Together, these discoveries give evidence that SAMHD1 regulation can be associated with cancers.…”

Section: Figurementioning

confidence: 95%

Roles of SAMHD1 in antiviral defense, autoimmunity and cancer

Zhang

Zhu

et al. 2017

Reviews in Medical Virology

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The enzyme, sterile α motif and histidine-aspartic acid domain-containing protein 1 (SAMHD1) diminishes infection of human immunodeficiency virus type 1 (HIV-1) by hydrolyzing intracellular deoxynucleotide triphosphates (dNTPs) in myeloid cells and resting CD4+ T cells. This dNTP degradation reduces the dNTP concentration to a level insufficient for viral cDNA synthesis, thereby inhibiting retroviral replication. This antiviral enzymatic activity can be inhibited by viral protein X (Vpx). The HIV-2/SIV Vpx causes degradation of SAMHD1, thus interfering with the SAMHD1-mediated restriction of retroviral replication. Recently, SAMHD1 has been suggested to restrict HIV-1 infection by directly digesting genomic HIV-1 RNA through a still controversial RNase activity. Here, we summarize the current knowledge about structure, antiviral mechanisms, intracellular localization, interferon-regulated expression of SAMHD1. We also describe SAMHD1-deficient animal models and an antiviral drug on the basis of disrupting proteasomal degradation of SAMHD1. In addition, the possible roles of SAMHD1 in regulating innate immune sensing, Aicardi-Goutières syndrome and cancer are discussed in this review.

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Aggressive CD8+ epidermotropic cutaneous T-cell lymphoma associated with homozygous mutation in SAMHD1

Cited by 22 publications

References 10 publications

Clonal evolution of acute myeloid leukemia from diagnosis to relapse

Clonal evolution of acute myeloid leukemia from diagnosis to relapse

MicroRNA-181 contributes to downregulation of SAMHD1 expression in CD4+ T-cells derived from Sèzary syndrome patients

Roles of SAMHD1 in antiviral defense, autoimmunity and cancer

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