- A single black ulcer in a child with acute lymphocytic leukemia. [Case Reports]
- ABAn Bras Dermatol 2016 Nov-Dec; 91(6):815-816
- Ecthyma gangrenosum is an uncommon dermatological manifestation characterized by round, indurated ulcers with a central necrotic black eschar and surrounding erythema. This report describes the case ...
Ecthyma gangrenosum is an uncommon dermatological manifestation characterized by round, indurated ulcers with a central necrotic black eschar and surrounding erythema. This report describes the case of a 5-year-old girl, affected by acute lymphocytic leukemia, presenting with a black eschar on her right thigh. Such lesions should always be correctly identified to avoid potentially fatal bacteraemia. Furthermore, because of its similar clinical presentation, cutaneous anthrax must be ruled out.
- Inferring a role for methylation of intergenic DNA in the regulation of genes aberrantly expressed in precursor B-cell acute lymphoblastic leukemia. [Journal Article]
- LLLeuk Lymphoma 2017 Jan 17; :1-12
- A complete understanding of the mechanisms involved in the development of pre-B ALL is lacking. In this study, we integrated DNA methylation data and gene expression data to elucidate the impact of a...
A complete understanding of the mechanisms involved in the development of pre-B ALL is lacking. In this study, we integrated DNA methylation data and gene expression data to elucidate the impact of aberrant intergenic DNA methylation on gene expression in pre-B ALL. We found a subset of differentially methylated intergenic loci that were associated with altered gene expression in pre-B ALL patients. Notably, 84% of these regions were also bound by transcription factors (TF) known to play roles in differentiation and B-cell development in a lymphoblastoid cell line. Further, an overall downregulation of eRNA transcripts was observed in pre-B ALL patients and these transcripts were associated with the downregulation of putative target genes involved in B-cell migration, proliferation, and apoptosis. The identification of novel putative regulatory regions highlights the significance of intergenic DNA sequences and may contribute to the identification of new therapeutic targets for the treatment of pre-B ALL.
- [The clinical features of patients with lymphoplasmacytic diseases harboring MyD88 L265P mutation]. [Journal Article]
- ZXZhonghua Xue Ye Xue Za Zhi 2016 Dec 14; 37(12):1054-1059
- Objective: To explore the clinical features of lymphoplasmacytic diseases with MyD88 L265P mutation. Methods: To analyze the distribution of MYD88 L265P mutation in patients with lymphoplasmacytic di...
Objective: To explore the clinical features of lymphoplasmacytic diseases with MyD88 L265P mutation. Methods: To analyze the distribution of MYD88 L265P mutation in patients with lymphoplasmacytic diseases by using of ARMS PCR-CE. Results: There were 25(30.9%) MyD88 L265P mutated patients in 81 patients. The mutation was frequently observed in 14 patients with WM (77.8%, 14/18), 2 patients with lymphoplasmacytic lymphoma (66.7%, 2/3), 1 acute lymphocytic leukemia patient (50.0%, 1/2), 3 multiple myeloma patients (30.0%, 3/10), 1 patient with monoclonal gammopathy of undetermined significance (25%, 1/4), 3 patients with chronic lymphocytic leukemia (13.0%, 3/23) and 1 lymphoma patient (4.8%, 1/21). 20 (80%, 20/25) patients were identified with IgM subtype. Compared with wild-type group of 56 cases, mutated patients were older (median age: 67 years vs 55 years, P< 0.001), with lower WBC count (median count: 5.23 × 10(9)/L vs 10.80 × 10(9)/L, P=0.001), lower HGB level (median count: 85 g/L vs 119 g/L, P<0.001). Conclusion: MyD88 L265P mutation was mainly observed in patients with IgM subtype lymphoplasmacytic diseases, and Waldenstrom' s macroglobulinemia was the most common disease. Compared with the wild-type group, patients with MyD88 L265P mutation were older and had lower WBC count, lower level of HGB. However, further studies were needed to test the prognostic value of MyD88 L265P mutation.
- Oncology's Trojan Horse: Using Viruses to Battle Cancer. [Journal Article]
- CPConsult Pharm 2016 Dec 01; 31(12):676-684
- In 2016, the American health care system was faced with more than 1.6 million new cases of cancer, and individuals older than 65 years of age will be affected disproportionately. Many older individua...
In 2016, the American health care system was faced with more than 1.6 million new cases of cancer, and individuals older than 65 years of age will be affected disproportionately. Many older individuals are poor candidates for traditional treatments (e.g., chemotherapy, radiation) because of actual or potential treatment-related adverse events. Researchers continuously look for novel therapeutic strategies, and an exciting new one is on the horizon: virotherapy. Viruses' ability to infect and kill human cells makes them promising cancer treatments. The greatest success has been seen in acute lymphocytic leukemia. To date, four genetically engineered oncolytic viruses have been approved globally by several countries' health regulatory agencies, but several challenges remain. Only one, talimogene laherparepvec (T-Vec), is available in the United States. Treatment-naive patients tend to respond better than patients receiving T-Vec as second-line therapy. Other good candidates for T-Vec include elderly patients who do not tolerate checkpoint inhibitors (the leading immunotherapy in advanced melanoma). Researchers continue to look for ways to increase oncolytic viruses' clinical potency. Once they do, these agents will become effective cancer therapy.
- Anti-CD22 CAR Therapy Leads to ALL Remissions. [Journal Article]
- CDCancer Discov 2017 Jan 09
- In a first-in-human trial of an anti-CD22 chimeric antigen receptor T-cell therapy in children and young adults with relapsed and refractory acute lymphocytic leukemia, researchers found that the imm...
In a first-in-human trial of an anti-CD22 chimeric antigen receptor T-cell therapy in children and young adults with relapsed and refractory acute lymphocytic leukemia, researchers found that the immunotherapeutic approach was not only feasible and safe, but also effective, leading to remissions in most patients. Infusions of higher numbers of T cells correlated with improved responses.
- Somatic MED12 Nonsense Mutation Escapes mRNA Decay and Reveals a Motif Required for Nuclear Entry. [Journal Article]
- HMHum Mutat 2017 Jan 05
- MED12 is a key component of the transcription-regulating Mediator complex. Specific missense and in-frame insertion/deletion mutations in exons 1 and 2 have been identified in uterine leiomyomas, bre...
MED12 is a key component of the transcription-regulating Mediator complex. Specific missense and in-frame insertion/deletion mutations in exons 1 and 2 have been identified in uterine leiomyomas, breast tumors, and chronic lymphocytic leukemia. Here, we characterize the first MED12 5' end nonsense mutation (c.97G>T, p.E33X) identified in acute lymphoblastic leukemia and show that it escapes nonsense-mediated mRNA decay (NMD) by using an alternative translation initiation site. The resulting N-terminally truncated protein is unable to enter the nucleus due to the lack of identified nuclear localization signal (NLS). The absence of NLS prevents the mutant MED12 protein to be recognized by importin-α and subsequent loading into the nuclear pore complex. Due to this mislocalization, all interactions between the MED12 mutant and other Mediator components are lost. Our findings provide new mechanistic insights into the MED12 functions and indicate that somatic nonsense mutations in early exons may avoid NMD.
- Expression and Regulation of Tal2 during Neuronal Differentiation in P19 Cells. [Journal Article]
- YZYakugaku Zasshi 2017; 137(1):61-71
- T-cell acute lymphocytic leukemia 2 (Tal2) is a gene encoding a member of the basic helix-loop-helix transcription factor family, which is essential for the normal development of the mouse brain. We...
T-cell acute lymphocytic leukemia 2 (Tal2) is a gene encoding a member of the basic helix-loop-helix transcription factor family, which is essential for the normal development of the mouse brain. We found that Tal2 was induced during neural differentiation in P19 cells, which are pluripotent mouse embryonal carcinoma cells that differentiate into the neural lineage upon both exposure to all-trans retinoic acid (atRA) and the formation of cell aggregation. Tal2 expression during neural differentiation in P19 cells was detected within 3 h after induction with atRA and retinoic acid receptor α (RARα). The atRA-RARα complex is known to bind to a characteristic retinoic acid response element (RARE) located in the promoter of target genes. We found a RARE-like element in the intron of Tal2. We also found a TATA-box-like element in the 5' region. The TATA-box-like element functioned as a core promoter, and TATA- box binding protein bound to this element upstream of Tal2 in P19 cells. The RARE-like element responded to atRA signaling that activated the transcription, and RARα was bound to this element in the intron of Tal2 in P19 cells. Furthermore, the interaction between these elements on Tal2 was confirmed in a chromatin immunoprecipitation assay. Because the neural differentiation of P19 cells mimics in part the development of the nervous system, P19 cells are useful for studying the mechanism underlying the role of Tal2 in neural differentiation. Further work is underway to clarify the function of Tal2 in neural differentiation using the differentiation system of P19 cells.
- Potent anti-leukemia activities of chimeric antigen receptor modified T cells against CD19 in Chinese patients with relapsed/refractory acute lymphocytic leukemia. [Journal Article]
- CCClin Cancer Res 2016 Dec 30
- CONCLUSIONS: This trial demonstrated potent anti-leukemia activities of CART19s in Chinese patients with R/R ALL. Disease relapse remained the main obstacle. However, patients with a high risk of relapse after CART19s might benefit from subsequent haploidentical hematopoietic stem cell transplantation.
- Glycogen Synthase Kinase-3β (GSK-3β) and Nuclear Factor Kappa-B (NFKB) in Childhood Acute Lymphoblastic Leukemia. [Journal Article]
- ACAdv Clin Exp Med 2016 Nov-Dec; 25(6):1139-1147
- CONCLUSIONS: These results suggest that GSK-3β may be a prognostic biomarker in childhood ALL.
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- Idelalisib-induced colitis and skin eruption mimicking graft-versus-host disease. [Journal Article]
- CJClin J Gastroenterol 2016 Dec 26
- CONCLUSIONS: High clinical suspicion and awareness of the histological features of idelalisib-associated colitis is important to distinguish it from potential mimickers such as GVHD and infectious colitis.