A global study for acute myeloid leukemia with RARG rearrangement.

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810).

Giant subcutaneous bronchogenic cyst in the intergluteal cleft region of an adult: a case report and literature review.

BACKGROUND: Bronchogenic cysts (BCs) are generally detected in the mediastinum, along the tracheobronchial tree, or in the lung parenchyma. Subcutaneous BCs are rare, but, when found, are usually small (< 3 cm) and detected in children. CASE PRESENTATION: In an unusual adult case, we treated a 52-year-old woman who presented with a mass in the left intergluteal cleft region. Ultrasonography showed a well-circumscribed hypoechoic lesion with posterior enhancement and internal echogenic foci within the mass. Color Doppler images showed no signals. Computed tomography showed the mass as a homogeneous, 6.8- × 6.3- × 5.1-cm soft tissue-attenuation lesion lodged in subcutaneous fatty tissue. Magnetic resonance imaging revealed a cystic lesion of similar dimensions with heterogeneous hyperintensity on both T1- and T2-weighted images. No contrast enhancement, solid components, or restricted diffusion foci were apparent. The cyst was completely excised, and histopathological evaluation indicated it was a BC. The patient's recovery was uneventful. CONCLUSIONS: BCs should be considered in the differential diagnosis of all subcutaneous cystic masses, regardless of their location and size and the patient's age.

Misdiagnosis and Delay of Diagnosis in Hemorrhagic Meningioma: A Case Series and Review of the Literature.

OBJECTIVE: To evaluate the clinicoradiologic characteristics of hemorrhagic meningiomas (HMs) that are missed or misdiagnosed on radiologic imaging studies. METHODS: Clinical and radiologic data from 6 patients with HM who were initially misdiagnosed were collected and recorded respectively. In addition, we performed a literature review for misdiagnosed HM and summarized the results. RESULTS: Five of the 6 patients with misdiagnosed HM were female, and 1 was male. Both computed tomography (CT) and magnetic resonance imaging were performed in 4 patients, and CT alone was performed in 2. On CT, the HM was heterogeneously hyperdense in 5 patients and isodense in 1 patient. In all 4 patients who underwent magnetic resonance imaging, the HM was mixed iso- and hypointense on T1-weighted imaging and heterogeneously hyperintense on T2-weighted imaging. Marked heterogeneous contrast enhancement was observed in 2 patients, strong rim enhancement in 1, and peripheral enhancement in 1. The dural tail sign was seen in only 1 patient. The initial radiologic misdiagnoses were subdural hematoma (n = 1), malignant glioma (n = 1), ruptured arterial aneurysm (n = 1), metastasis (n = 2), and uncertain (n = 1). In the literature review, 22 cases of HM diagnostic error were collected. The main misdiagnoses were subdural hematoma (27.3%), traumatic hematoma (13.6%), vascular anomaly (13.6%), malignant glioma (4.5%), and metastasis (4.5%). CONCLUSIONS: Our study showed that in patients with HM with inadequate imaging evaluation, a small tumor associated with massive hematoma and atypical imaging features was more likely to be misdiagnosed.

Genomic and Transcriptomic Characterization of Natural Killer T Cell Lymphoma.

Natural killer/T cell lymphoma (NKTCL) is an aggressive and heterogeneous entity of non-Hodgkin lymphoma, strongly associated with Epstein-Barr virus (EBV) infection. To identify molecular subtypes of NKTCL based on genomic structural alterations and EBV sequences, we performed multi-omics study on 128 biopsy samples of newly diagnosed NKTCL and defined three prominent subtypes, which differ significantly in cell of origin, EBV gene expression, transcriptional signatures, and responses to asparaginase-based regimens and targeted therapy. Our findings thus identify molecular networks of EBV-associated pathogenesis and suggest potential clinical strategies on NKTCL.

Aspirin inhibits proliferation and induces apoptosis of multiple myeloma cells through regulation of Bcl-2 and Bax and suppression of VEGF.

OBJECTIVES: Aspirin (ASA) has been frequently used for thromboprophylaxis in patients with multiple myeloma (MM) when treated with thalidomide or lenalidomide. Despite the well-recognized chemopreventive role of ASA in some solid tumors particularly for colon cancer, whether ASA displays the antimyeloma activity remains unclear. METHODS: MM1.S and RPMI-8226 cell lines harboring K-Ras and N-Ras mutation, respectively, were treated with various concentrations of ASA for different hours. The cell proliferation and apoptosis were performed to explore the effects of ASA on myeloma. Then, the exact mechanisms governing ASA's antimyeloma were explored by qRT-PCR and Western blot. Also, the effect of ASA on tumor growth was observed in NOD/SCID mice bearing myeloma xenografts. RESULTS: ASA of 0-10 mm concentration inhibits proliferation MM1.S and RPMI-8226 cells in time- and dose-dependent manner. The myeloma cells exposed to ASA treatment displayed concentration-dependent apoptosis, which was closely associated with activation of caspases, upregulation of Bax, and downregulation of Bcl-2 and VEGF. Study in vivo revealed that ASA administration retarded the tumor growth accompanying the survival time of mice bearing myeloma xenografts. CONCLUSIONS: ASA exerted antiproliferative and pro-apoptotic action in myeloma cells in vitro and delayed the growth of human myeloma cells in vivo. The underlying mechanisms were ascribed to regulation of Bcl-2 and Bax and suppression of VEGF.

[Differentiation of human umbilical cord blood mesenchymal stem cells toward neurons induced by baicalin in vitro].

OBJECTIVE: To study the possibility and mechanism by which the human umbilical blood mesenchymal stem cells (MSCs) are induced to differentiate into neuron in vitro by baicalin, a kind of flavonoid isolated from an important medicinal plant Scutellariae Radix. METHODS: Human cord blood was obtained via sterile procedure with 20 U/ml of preservative-free heparin. MSCs were isolated by the two-step assay of gelatin sedimentation plus Ficoll centrifugation separation, purified and amplified in the liquid culture medium. According to the kind of antioxidants, the experiment was conducted in five groups: induction group, control group I, control group II, control group III and control group IV. Five subgroups of MSCs amplificated ex vivo for 2 weeks in each group were induced by the media containing baicalin (BC, 200 - 400 micromol/L) or baicalin-free for seven days. The media consisted of induction medium (DMEM plus 200 - 400 micromol/L of baicalin) and post-induction medium (DMEM plus 200 - 400 micromol/L of baicalin, B27). The expression of neuronal or glia specific markers was evaluated by using indirect immunofluorescence cytochemistry staining. The percentage of differentiated cells and living cells was measured by Hoechest 33,258 staining assay. RESULTS: After induction for 7 days, MSCs displayed neuronal morphologies, such as pyramidal cell bodies and processes formed extensive network. The undifferentiated cells did not exhibit a neuronal or glial phenotype, while the differentiating cells expressed NSE and MAP-2, the specific markers of neuron, but did not express GFAP, the specific marker of glia on the seventh day after induced by baicalin. The percentage of NSE and MAP-2 expressed on the seventh day after induced by baicalin was (76.3 +/- 9.2)% and (78.5 +/- 5.5)%, respectively, which was significantly higher compared with control group I, control group II and control group III (P < 0.01), respectively. In addition, the ratio of living cells after induced for seven days in the BC group was (85.3 +/- 4.8)%, which increased significantly compared with control group I, control group II and control group III (P < 0.01), respectively. CONCLUSIONS: Baicalin may induce the umbilical blood MSCs to neuron or neuron-alike cells in vitro in a moderate and stable manner. The mechanism of such an induction may be related with its controlling the activity of NF-kappaB which regulates the production of many kinds of cytokines, such as brain-derived neurotrophic factor (BDNF), etc.

[Role of tissue factor pathway inhibitor-2 in ovarian tumor migration and invasion].

BACKGROUND & OBJECTIVE: Human tissue factor pathway inhibitor-2 (TFPI-2) is a newly discovered serine protease inhibitor, which inhibits plasmin, trypsin, matrix metalloproteinase (MMPs), but not urokinase, tissue-type plasminogen activators and thrombin. Earlier studies have shown that the production of TFPI-2 is downregulated during the progression of various cancers. The aim of this study was to elucidate the relationship between TFPI-2 expression and ovarian tumor migration and invasion. METHODS: Human TFPI-2 expression vector pBos-Cite-neo/TFPI-2 was transfected into ovarian tumor cells line A2780. After the transfected cells were screened by G418, transfected and nontransfected cells were examined for TFPI-2 mRNA and protein by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. The number of transfected or nontransfected cells passing through membrane of Boyden chamber was counted as the basis assessing tumor cells migratory and invasive behaviors. RESULTS: Expression of mRNA and protein of TFPI-2 were confirmed in transfected cells. In invasion assay, the number of TFPI-2-expressing cells to traverse a Matrigel-coated membrane was obviously decreased compared with that of nonexpressing cells (59.3+/-6.5 versus 109.7+/-5.5, P< 0.01); while in migration assay, no significant difference was observed between transfected and nontransfected cells (114.7+/-8.6 versus 127.3+/-7.1, P >0.05). CONCLUSION: Expression of TFPI-2 may strongly inhibit the invasive ability of ovarian tumor cells in vitro, but has no effect on the migratory ability, which provides an experimental basis for treating human ovarian tumor with gene therapy.