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2.
Genomics ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33639237

RESUMO

In this study, 18 MACPF genes (RpMACPF) were identified and classed into three types (Macrophage-expressed gene 1, Apextrin, and MACPF domain contain protein) based on gene structure and phylogenetic relationship in R. philippinarum. The length of RpMACPF proteins varied from 287 to 785 amino acids. The molecular weights and Theoretical PI values ranged from 3.2 kDa to 8.7 kDa and 4.7 to 8.6, respectively. RNA-seq data analysis revealed that 14 of 18 RpMACPF genes were highly expressed at the pediveliger larvae stage indicate RpMACPF might contribute to the early development and metamorphosis processes of the R. philippinarum. Besides, we found RpMACPF genes were significantly regulated by pathogen-associated molecular patterns (PAMPs) and Vibrio parahemolyticus, which indicates RpMACPF genes may play significant roles in response to invading pathogens. The results obtained in this work will provide valuable insight into the immune function of MACPF gene in R. philippinarum.

3.
Sci Rep ; 11(1): 4057, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33603080

RESUMO

The advanced biomimetic mineralization technology was applied to protect the Botulinum neurotoxin type D, and the processing of the mineralization granule of botulinum toxin type D was successfully screened. The loss of activity of the toxin protein at different temperatures and the destructive strength of the gastrointestinal tract against the toxin were determined biologically. The lethal toxicity of the mineralized toxin to wild rodents was determined by median lethal dose. Protective tests at different temperatures showed that the preservation period of botulinum toxin type D mineralized sample 2 was significantly higher than that of the control group at three different temperatures, and its toxicity loss was significantly reduced. The damage intensity of the mineralized toxin to the gastrointestinal contents of plateau zokor and plateau pika was significantly reduced. The minimum lethal doses of the mineralized toxin particles to plateau zokor, plateau pika, and mice were 5200, 8,600,000, and 25,000 MLD/kg. These results showed that biomimetic mineralization could greatly improve the thermal stability of botulinum toxin type D and reduce the damaging effect of the gastrointestinal contents of target animals to botulinum toxin type D. The mineralized toxin could be used to control the population density of urban rodents. This research provides new insights into the protection of toxin protein substances.

4.
Genomics ; 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33626340

RESUMO

Ruditapes philippinarum is an economically important marine shellfish aquaculture species, and it has the ability to regenerate its siphons. To gain a greater understanding of the molecular mechanisms at work during siphon regeneration and to provide evidence for morphological regeneration, we examined transcriptome responses of siphon tissue of R. philippinarum during regeneration and observed regenerative siphons under the stereomicroscope. The overall process of siphon regeneration was dissected based on the morphological changes of siphon and the identification of up-regulated key differentially expressed genes (DEGs). The protein biosynthesis and metabolism played important roles in wound healing and siphon regeneration of R. philippinarum. Transcriptomic analysis identified the Wnt and TGF-ß signaling pathways by focusing on the function and expression pattern of genes in these pathways during siphon regeneration. In addition, we carried out a genome-wide identification and phylogenetic analysis of TGF-ß superfamily in R. philippinarum. The expression profiles of the TGF-ß superfamily genes were analyzed in eight adult tissues (adductor muscle, mantle, foot, gill, siphon, digestive gland, gonad, and labial palp) and regenerative siphon. This study shed light on the process of morphological regeneration and regenerative mechanism of siphon of R. philippinarum.

6.
Am J Surg Pathol ; 45(2): 277-285, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33428338

RESUMO

A subset of Spitz tumors is associated with a copy number increase of chromosome 11p and activating mutations of HRAS. These aberrations have been reported to occur in association with desmoplastic Spitz nevi. Little is known to what extent 11p gains can also be found in nondesmoplastic tumors. To learn more about the spectrum of microscopic and cytogenetic changes that can be seen in Spitz lesions in association with 11p gains, we reviewed the clinical and pathologic features of 40 cases. Patient ages ranged from 3 to 75 years. The most common anatomic site was the head and neck region, followed by the upper extremities. Prominent desmoplasia was present in 10 cases. Seven tumors lacked significant stromal fibrosis. Twenty tumors were mitotically active. Novel microscopic features encountered in a few cases include a tumor with a polypoid silhouette and papillomatous surface and rare atypical tumors with a deep bulbous growth pattern. Among 36 cases analyzed by single-nucleotide polymorphism array or comparative genomic hybridization, 28 tumors had gains of the entire or near-entire p-arm of chromosome 11 with no other coexisting unbalanced genomic aberration. Eight cases had additional changes; 6 of these with 1 additional aberration per case, and 2 cases had several chromosomal aberrations. We also examined a subset of tumors by fluorescence in situ hybridization for the HRAS gene locus (11p15.5). All tumors were fluorescence in situ hybridization-positive. In conclusion, we expand the spectrum of pathologic findings associated with Spitz tumors with 11p gains. This cytogenetic aberration is not restricted to desmoplastic Spitz nevi. It can also be seen in nondesmoplastic and papillomatous lesions and atypical melanocytic tumors with a deep bulbous growth. We also document that in some Spitz tumors additional cytogenetic aberrations may be found, the significance of which remains to be determined.


Assuntos
Cromossomos Humanos Par 11/genética , Nevo de Células Epitelioides e Fusiformes/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Aberrações Cromossômicas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nevo de Células Epitelioides e Fusiformes/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Cutâneas/patologia , Adulto Jovem
7.
J Virol ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504605

RESUMO

Peste des petits ruminants virus (PPRV) is an important pathogen that seriously influences the productivity of small ruminants worldwide. PPRV has evolved several mechanisms to evade IFN-I responses. We report that a novel microRNA in goat PBMCs, novel miR-3, was upregulated by PPRV to facilitate virus infection. Furthermore, PPRV V protein alone was sufficient to induce novel miR-3 expression, and NF-κB and p38 pathway may involved in the induction of novel miR-3 during PPRV infection. Importantly, we demonstrated that novel miR-3 was a potent negative regulator of IFN-α production by targeting IRAK1, which resulted in the enhancement of PPRV infection. In addition, we found that PPRV infection can activated ISGs through IFN independent and IRF3 dependent pathway. Moreover, our data revealed that novel miR-3 mediated regulation of IFN-α production may involve in the differential susceptibility between goat and sheep to PPRV. Taken together, our findings identified a new strategy taken by PPRV to escape IFN-I-mediated antiviral immune responses by engaging cellular microRNA and, thus, improve our understanding of its pathogenesis.IMPORTANCE: Peste des petits ruminants virus (PPRV) induce in the hosts a transient but severe immunosuppression, which threatens both small livestock and endangered susceptible wildlife populations in many countries. Despite extensive research has been explored, the mechanism underlying PPRV immune system evasion remains elusive. Our data provided the first direct evidence that novel microRNA-3 (novel miR-3) feedback inhibits type I IFN signaling when goat PBMCs are infected with PPRV vaccine strain N75/1, thus promoting the infection. In this study, the target of novel miR-3, IRAK1, which are important for PPRV-induced type I IFN production, have also been found. Moreover, we identified NF-κB and p38 pathways may involve in novel miR-3 induction in response to PPRV infection. Taken together, our research has provided new insight into understanding the effects of miRNA on host-virus interactions, and revealed a potential therapeutic target for antiviral intervention.

8.
Nat Commun ; 12(1): 338, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436578

RESUMO

Stably acquired mutations in hematopoietic cells represent substrates of selection that may lead to clonal hematopoiesis (CH), a common state in cancer patients that is associated with a heightened risk of leukemia development. Owing to technical and sample size limitations, most CH studies have characterized gene mutations or mosaic chromosomal alterations (mCAs) individually. Here we leverage peripheral blood sequencing data from 32,442 cancer patients to jointly characterize gene mutations (n = 14,789) and mCAs (n = 383) in CH. Recurrent composite genotypes resembling known genetic interactions in leukemia genomes underlie 23% of all detected autosomal alterations, indicating that these selection mechanisms are operative early in clonal evolution. CH with composite genotypes defines a patient group at high risk of leukemia progression (3-year cumulative incidence 14.6%, CI: 7-22%). Multivariable analysis identifies mCA as an independent risk factor for leukemia development (HR = 14, 95% CI: 6-33, P < 0.001). Our results suggest that mCA should be considered in conjunction with gene mutations in the surveillance of patients at risk of hematologic neoplasms.


Assuntos
Aberrações Cromossômicas , Evolução Clonal/genética , Mutação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Neoplasias Hematológicas/genética , Humanos , Pessoa de Meia-Idade , Mosaicismo , Neoplasias/genética , Medição de Risco , Seleção Genética , Adulto Jovem
9.
Mol Med Rep ; 23(3): 1, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33495835

RESUMO

The activation of chimeric antigen receptor (CAR)­T cells can lead to persistently high levels of programmed cell death 1 (PD­1) antigen and eventually causes the exhaustion of T cells. The effectiveness of CAR­T cells targeting C­type lectin­like molecule­1 (CLL­1) combined with PD­1 silencing therapy for acute myeloid leukemia (AML) was evaluated in the present study. CLL­1 levels in primary AML bone marrow samples was examined using flow cytometric analysis. We designed a CLL­1 CAR­T, containing CLL­1­specific single­chain variable fragment, CD28, OX40, CD8 hinge and TM and CD3­Î¶ signaling domains. CLL­1 CAR­T with PD­1 silencing was constructed. It was confirmed that CLL­1 is expressed on the surface of AML cells. CLL­1 CAR­T showed specific lysing activity against CLL­1+ AML cells. PD­1 silencing enhanced the killing ability of CLL­1 CAR­T. Furthermore, it was found that CAR­T derived from healthy donor T cells was more effective in killing THP­1 cells (a human acute monocytic leukemia cell line) than those from patient­derived T cells. These results indicated that CLL­1 CAR­T and PD­1 knockdown CLL­1 CAR­T could be used as a potential immunotherapy to treat relapsed or refractory AML.

10.
Medicine (Baltimore) ; 100(2): e24047, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466157

RESUMO

INTRODUCTION: Post-transplant lymphoproliferative disease (PTLD) is a series of proliferative diseases of the lymphatic system. Among patients receiving hematopoietic stem cell transplantation (HSCT), PTLD is a prevalent complication that severely affects rates of survival. Ultrasound plays an essential role in the early diagnosis of PTLD. Contrast-enhanced ultrasonography (CEUS) and CEUS-guided biopsy are critical procedures for tumor diagnosis. PATIENT CONCERNS: Herein, we report the case of a 40-year-old male patient with acute lymphoblastic leukemia who received HSCT more than 1 year ago. Sonography revealed a small hypoechoic nodule in the liver four months after HSCT. Eight months after HSCT, larger and more nodules were observed via ultrasound; CT was used to identify the lesions. DIAGNOSES: CEUS and CEUS-guided biopsy were performed, and the pathological diagnosis was PTLD. INTERVENTIONS: The final clinical diagnosis was PTLD, and cyclophosphamide, epirubicin, and dexamethasone were administered as chemotherapy. OUTCOMES: The patient was discharged after his condition improved. CONCLUSION: Ultrasound can be used to effectively detect lesions of PTLD early after HSCT. Furthermore, CEUS and CEUS-guided biopsy were effective for early confirmatory diagnoses of PTLD after HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Adulto , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Humanos , Transtornos Linfoproliferativos/diagnóstico por imagem , Masculino , Ultrassonografia/métodos
11.
Clin Cancer Res ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504553

RESUMO

PURPOSE: The World Trade Center (WTC) attack of September 11, 2001 created an unprecedented environmental exposure to known and suspected carcinogens. High incidence of multiple myeloma and precursor conditions has been reported among first responders to the WTC disaster. To expand on our prior screening studies, and to characterize the genomic impact of the exposure to known and potential carcinogens in the WTC debris, we were motivated to perform whole-genome sequencing (WGS) of WTC first responders and recovery workers who developed a plasma cell disorder after the attack. EXPERIMENTAL DESIGN: We performed WGS of nine CD138-positive bone marrow mononuclear samples from patients who were diagnosed with plasma cell disorders after the WTC disaster. RESULTS: No significant differences were observed in comparing the post-WTC driver and mutational signature landscapes with 110 previously published WGSs from 56 patients with multiple myeloma and the CoMMpass WGS cohort (n = 752). Leveraging constant activity of the single-base substitution mutational signatures 1 and 5 over time, we estimated that tumor-initiating chromosomal gains were windowed to both pre- and post-WTC exposure. CONCLUSIONS: Although limitations in sample size preclude any definitive conclusions, our findings suggest that the observed increased incidence of plasma cell neoplasms in this population is due to complex and heterogeneous effects of the WTC exposure that may have initiated or contributed to progression of malignancy.

12.
Bioorg Med Chem Lett ; 34: 127758, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33359608

RESUMO

The ATP-adenosine pathway has been recently identified as an attractive immune-oncology target and several drug candidates have been entered clinic trials. Inspired by the report of the first small-molecule CD73inhibitor AB680, we describe the discovery of natural product ellagic acid as a dual CD73 and CD39 inhibitor with an IC50 value of 1.85 ± 0.21 µM and 0.50 ± 0.22 µM, respectively. The result of cytotoxicity assays indicated that ellagic acid is a valuable lead compound with low cytotoxicity effect for immune therapy.

13.
Genes Chromosomes Cancer ; 60(1): 43-48, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32920865

RESUMO

Evolution of poorly differentiated chordoma from conventional chordoma has not been previously reported. We encountered a case of a poorly differentiated chordoma with evidence of whole-genome doubling arising from a SMARCB1-deficient conventional chordoma. The tumor presented as a destructive sacral mass in a 43-year-old man and was comprised of a highly cellular poorly differentiated chordoma with small, morphologically distinct nodules of conventional chordoma accounting for <5% of the total tumor volume. Immunohistochemistry (IHC) revealed both components were strongly reactive for brachyury and lacked normal staining for INI1. Single nucleotide polymorphism (SNP) array analysis identified multiple genomic imbalances in the conventional component, including deletions of 1p, 3p, and 22q (involving SMARCB1) and loss of chromosomes 5 and 15, while the poorly differentiated component exhibited the same aberrations at a more profound level with additional loss of chromosome 4, low level focal deletion of 17p (involving TP53), and tetraploidy. Homozygous deletion of SMARCB1 was present in both components. Fluorescence in situ hybridization (FISH) analysis confirmed the relevant deletions in both components as well as genome doubling in the poorly differentiated tumor. This case suggests that SMARCB1 loss is an early event in rare conventional chordomas that could potentially evolve into poorly differentiated chordoma through additional genomic aberrations such as genome doubling. Further studies with additional patients will be needed to determine if genome doubling is a consistent pathway for evolution of poorly differentiated chordoma.

14.
Am J Surg Pathol ; 45(1): 77-92, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32889887

RESUMO

Although diagnosis of high-grade uterine mesenchymal tumors (UMTs) exhibiting classic morphologic features is straightforward, diagnosis is more challenging in tumors in which prototypical features are poorly developed, focal, and/or coexist with features seen in other neoplasms. Here, we sought to define the repertoire of somatic genetic alterations in diagnostically challenging UMTs with myomelanocytic differentiation, including some reported as perivascular epithelioid cell tumors (PEComas). In 17 samples from 15 women, the tumors were histologically heterogenous. Immunohistochemical expression of at least 1 melanocytic marker (HMB45, Melan-A, or MiTF) was identified in all tumors, and of myogenic markers (desmin or smooth muscle actin) in most tumors. Targeted massively parallel sequencing revealed several genetic alterations, most commonly in TP53 (41% mutation, 12% deletion), TSC2 (29% mutation, 6% deletion), RB1 (18% deletion), ATRX (24% mutation), MED12 (12% mutation), BRCA2 (12% deletion), CDKN2A (6% deletion) as well as FGFR3, NTRK1, and ERBB3 amplification (each 6%). Gene rearrangements (JAZF1-SUZ12; DNAJB6-PLAG1; and SFPQ-TFE3) were identified in 3 tumors. Integrating histopathologic, immunohistochemical, and genetic findings, tumors from 4 patients were consistent with malignant PEComa (1 TFE3-rearranged); 6 were classified as leiomyosarcomas; 3 showed overlapping features of PEComa and other sarcoma types (leiomyosarcoma or low-grade endometrial stromal sarcoma); and 2 were classified as sarcoma, not otherwise specified. Our findings suggest that diagnostically challenging UMTs with myomelanocytic differentiation represent a heterogenous group of neoplasms which harbor a diverse repertoire of somatic genetic alterations; these genetic alterations can aid classification.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Sarcoma/diagnóstico , Neoplasias Uterinas/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/análise , Feminino , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Neoplasias de Células Epitelioides Perivasculares/classificação , Neoplasias de Células Epitelioides Perivasculares/genética , Sarcoma/classificação , Sarcoma/genética , Neoplasias Uterinas/classificação , Neoplasias Uterinas/genética
15.
Clin Cancer Res ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33272981

RESUMO

PURPOSE: Selpercatinib and pralsetinib induce deep and durable responses in advanced RET fusion-positive lung and thyroid cancer patients. RET fusion testing strategies with rapid and reliable results are critical given recent FDA approval. Here, we assess various clinical assays in a large pan-cancer cohort. EXPERIMENTAL DESIGN: Tumors underwent DNA-based next generation sequencing (NGS) with reflex to RNA-based NGS if no mitogenic driver or if a RET structural variant of unknown significance (SVUS) were present. Canonical DNA-level RET fusions and RNA-confirmed RET fusions were considered true fusions. Break-apart fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) performance were assessed in subgroups. RESULTS: 171 of 41,869 patients with DNA NGS harbored RET structural variants, including 139 canonical fusions and 32 SVUS. 12/32 (37.5%) SVUS were transcribed into RNA-level fusions, resulting in 151 oncogenic RET fusions. The most common RET fusion-positive tumor types were lung (65.6%) and thyroid (23.2%). The most common partners were KIF5B (45%), CCDC6 (29.1%), and NCOA4 (13.3%). DNA NGS showed 100% (46/46) sensitivity and 99.6% (4459/4479) specificity. FISH showed 91.7% (44/48) sensitivity, with lower sensitivity for NCOA4-RET (66.7%, 8/12). 87.5% (7/8) of RET SVUS negative for RNA-level fusions demonstrated rearrangement by FISH. The sensitivity of IHC varied by fusion partner: KIF5B sensitivity was highest (100%, 31/31), followed by CCDC6 (88.9%, 16/18) and NCOA4 (50%, 6/12). Specificity of RET IHC was 82% (73/89). CONCLUSIONS: While DNA sequencing has high sensitivity and specificity, RNA sequencing of RET SVUS is necessary. Both FISH and IHC demonstrated lower sensitivity for NCOA4-RET fusions.

17.
Zoolog Sci ; 37(6): 505-511, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33269865

RESUMO

Through population expansion and accidental or deliberate introduction, prey commonly encounter novel predators they had never seen before. Several studies have shown that animals can generalize their learned recognition of a familiar predator to novel ones according to predators' identical or similar features. This process in fish mainly depends on the visual and chemosensory cues they receive. However, there is a lack of understanding of the different effects of these two cues. Topmouth gudgeons (Pseudorasbora parva) that had never seen turtles were captured and used as the subjects, and three freshwater turtles of different genera were used as predators. Before and after using one turtle for predator training treatment of topmouth gudgeons, fish responses to visual and chemosensory cues of each turtle were tested and recorded, and it was found that predator training promoted topmouth gudgeons' recognition of the risks represented by visual cues of all three turtles and by chemosensory cues of the turtle that were used in training. These results further verify the generalization of predator recognition in fish and indicate that visual cues have a more extensive effect on fish than chemosensory cues in identifying novel predators, especially predators that are distantly related to the familiar threats.

18.
Microb Biotechnol ; 2020 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-33369229

RESUMO

The previous studies have reported that the mammalian gut microbiota is a physiological consequence; nonetheless, the factors influencing its composition and function remain unclear. In this study, to evaluate the contributions of the host and environment to the gut microbiota, we conducted a sequencing analysis of 16S rDNA and shotgun metagenomic DNA from plateau pikas and yaks, two sympatric herbivorous mammals, and further compared the sequences in summer and winter. The results revealed that both pikas and yaks harboured considerably more distinct communities between summer and winter. We detected the over-representation of Verrucomicrobia and Proteobacteria in pikas, and Archaea and Bacteroidetes in yaks. Firmicutes and Actinobacteria, associated with energy-efficient acquisition, significantly enriched in winter. The diversity of the microbial community was determined by the interactive effects between the host and season. Metagenomic analysis revealed that methane-metabolism-related pathway of yaks was significantly enriched in summer, while some pathogenic pathways were more abundant in pikas. Both pikas and yaks had a higher capacity for lipid degradation in winter. Pika and yak shared more OTUs when food shortage occurred in winter, and this caused a convergence in gut microbial composition and function. From winter to summer, the network module number increased from one to five in pikas, which was different in yaks. Our study demonstrates that the host is a dominant factor in shaping the microbial communities and that seasonality promotes divergence or convergence based on dietary quality across host species identity.

19.
Cell Death Dis ; 11(12): 1062, 2020 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-33311488

RESUMO

Reversing the highly immunosuppressive tumor microenvironment (TME) is essential to achieve long-term efficacy with cancer immunotherapy. Despite the impressive clinical response to checkpoint blockade in multiple types of cancer, only a minority of patients benefit from this approach. Here, we report that the oncolytic virus M1 induces immunogenic tumor cell death and subsequently restores the ability of dendritic cells to prime antitumor T cells. Intravenous injection of M1 disrupts immune tolerance in the privileged TME, reprogramming immune-silent (cold) tumors into immune-inflamed (hot) tumors. M1 elicits potent CD8+ T cell-dependent therapeutic effects and establishes long-term antitumor immune memory in poorly immunogenic tumor models. Pretreatment with M1 sensitizes refractory tumors to subsequent checkpoint blockade by boosting T-cell recruitment and upregulating the expression of PD-L1. These findings reveal the antitumor immunological mechanism of the M1 virus and indicated that oncolytic viruses are ideal cotreatments for checkpoint blockade immunotherapy.

20.
J Hematol ; 9(4): 140-146, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33224395

RESUMO

A 75-year-old man with no prior history of cytotoxic therapy presented with increasing fatigue and shortness of breath. He was found to have a new onset of pancytopenia, and chest X-ray showed severe pneumonia. Additional radiology exam revealed pan-lobar pneumonia, pleural effusion, generalized lymphadenopathy and mild splenomegaly. Bone marrow and mediastinal lymph node biopsy from the bilateral level 4 lymph nodes were performed to evaluate the cause of pancytopenia and generalized lymphadenopathy, respectively. Histologic sections of lymph nodes were consistent with angioimmunoblastic T-cell lymphoma (AITL), and bone marrow biopsy showed low level involvement by AITL. Background trilineage hematopoiesis showed features suggestive of myelodysplastic syndrome (MDS) with karyotyping showing deletion 20q; however, interpretation of dysplasia and exclusion of reactive process was difficult due to the presence of severe infection, administration of multiple medications and multiorgan failure. Therefore, to further evaluate the possibility of concomitant myeloid neoplasm, we performed flow cytometry sorting of bone marrow aspirate to isolate the myeloid cell population from the abnormal T-cell population, and comprehensive genomic profiling was performed in each population separately. Flow-sorted myeloid population showed three somatic mutations involving DNMT3A and BCORL1, supporting the diagnosis of MDS in conjunction with the presence of deletion 20q. Flow sorted abnormal T-cell population showed six somatic mutations consistent with AITL, involving Ras homolog gene family member A (RHOA), TET2, DNMT3A, NOTCH2 and XPO1. These two sorted populations shared the DNMT3A p.N612Rfs*26 mutation, and the variants unique to one sorted population were confirmed to be completely absent in another sorted population by manual review of the sample. These findings suggested that the two neoplasms were clonally related and were sharing a common hematopoietic progenitor precursor, but underwent clonal divergence over time, leading to the development of two distinct neoplastic processes of T and myeloid lineages. This illustrates a rare case of concurrent diagnosis of AITL and de novo MDS and reliable genomic assessment was performed at the time of diagnosis to detect mutations in each neoplastic process without contamination. Further studies are needed to assess hypomethylating agents as potential therapy options for these patients.

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