Journal: Epigenetics

Article Title: The combination of dimethoxycurcumin with DNA methylation inhibitor enhances gene re-expression of promoter-methylated genes and antagonizes their cytotoxic effect

doi: 10.1080/15592294.2016.1226452

Figure Lengend Snippet: Effect of simultaneous treatment with DAC and DMC on apoptosis induction in leukemia cells. a. CEM leukemia cells were treated with different concentrations of DAC, DMC, and the combination for 48 h and apoptosis induction was quantified as described under methods. The left, middle, and right panels: we used 250 nM, 500 nM, and 1000 nM of DAC in combination with different concentrations of DMC, respectively. b. Jurkat leukemia cells were treated with DAC, DMC, and the combination, similar to the treatment to CEM cells. In all experiments, data represent the mean ± SD for 3 replicates. c. Analysis of the synergistic and antagonistic effects of the combination on apoptosis induction. The combination index (CI) was calculated by CalcuSyn software for dose-effect analysis in CEM cells (left panel) and Jurkat cells (right panel). The combinations used were fixed concentrations of DAC with variable concentrations of DMC (250, 500, 1000 nM). d. Analysis of the synergistic and antagonistic effects of the combination on apoptosis induction in BMNC derived from MDS (left panel) and AML patients (right panel). ‘1′ indicates 100 nM DAC + 250 nM DMC, ‘2′ indicates 100 nM DAC + 500 nM DMC, ‘3′ indicates 250 nM DAC + 250 DMC, and ‘4′ indicates 250 nM DAC + 500 nM DMC. CI values equal to 1 are represented by the dashed line and considered additive, values greater than 1 are antagonistic, and values lower than 1 are synergistic.

Article Snippet: Frozen acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) bone marrow mononuclear cells (BMNC) were purchased from Allcells (Alameda, CA).

Techniques: Software, Derivative Assay

Journal: Epigenetics

Article Title: The combination of dimethoxycurcumin with DNA methylation inhibitor enhances gene re-expression of promoter-methylated genes and antagonizes their cytotoxic effect

doi: 10.1080/15592294.2016.1226452

Figure Lengend Snippet: The combination of DMC and DAC enhances gene expression of promoter-methylated genes. CEM cells treated with the single drugs and the combination for 24 h and gene expression of p15 (a) and CDH-1 (b) was quantified by RT-PCR as described under Materials and methods. c. BMNC from AML and MDS patients were treated with the single drugs and the combination for 24 h and gene expression of p15 and CDH-1 was quantified. The alphanumeric characters represent the name of the drug and the concentration in nM, where ‘D’ represents DAC and ‘M’ represents DMC. For instance, D100 represents DAC 100 nM and D250 + M500 represents the combination of DAC 250 nM and DMC 500 nM. Data represent the mean ± SD for 3 replicates. * indicates a significant difference from the control at P < 0.05. d. CEM cells treated with the single drugs and the combination for 24 h and the protein expression of p15 and CDH-1 was quantified by Western blotting. D + M250 indicates the combination of 250 nM DAC and 250 nM of DMC. D + M500 indicates the combination of 250 nM DAC and 500 nM DMC.

Article Snippet: Frozen acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) bone marrow mononuclear cells (BMNC) were purchased from Allcells (Alameda, CA).

Techniques: Expressing, Methylation, Reverse Transcription Polymerase Chain Reaction, Concentration Assay, Western Blot

Journal: Blood Advances

Article Title: Clinical, molecular, and prognostic comparisons between CCUS and lower-risk MDS: a study of 187 molecularly annotated patients

doi: 10.1182/bloodadvances.2020003976

Figure Lengend Snippet: Molecular characteristics and survival outcomes in patients with clonal cytopenias of undetermined significance, lower-risk myelodysplastic syndromes, and lower-risk chronic myelomonocytic leukemia. (A) Split bean plot demonstrating the 6 most common mutations in both CCUS and LR-MDS and their respective VAFs. (B) Bar graph of CCUS and LR-MDS demonstrating the 10 most frequent mutations in all 188 patients and the percentage of patients with that mutation. (C) Kaplan-Meier OS estimate in CCUS and LR-MDS patients, censored at 10 years of follow-up. (D) Kaplan-Meier leukemia-free survival estimate in CCUS, LR-MDS, and LR-CMML patients, censored at 10 years of follow-up. (E) Distribution of survival and progression outcomes in LR-MDS, LR-CMML, and CCUS patients.

Article Snippet: The authors thank the Mayo Clinic Center for Individualized Medicine for sponsoring the clonal hematopoiesis clinic and the Henry J. Predolin leukemia fund for developing the myelodysplastic syndrome/acute myeloid leukemia biorepository.

Techniques: Mutagenesis

Journal: Transplantation and cellular therapy

Article Title: NK Cell Adoptive Immunotherapy of Cancer: Evaluating Recognition Strategies and Overcoming Limitations

doi: 10.1016/j.bbmt.2020.09.030

Figure Lengend Snippet: Top left, in red: NK cells recognize tumor targets that lack MHC, as this prevents the inhibitory response mediated by KIR. Several tumors down-regulate MHC in response to T cell immune pressure. The same pathway does not become activated in the setting of allogeneic NK cells and is only engaged when NK cell effectors recognize self MHC. Bottom, in blue: NK cell activating receptor ligands are expressed by numerous malignancies [45-60,62,242-247], and these tumors engage NK-activating receptors, some of which associate with ITAM-containing DAP10 and DAP12 to mediate NK cell activation via proteins such as Vav1 and PLCγ2. Top right, in green: NK cells are the principal effectors of ADCC, mediating tumor lysis in settings when antibodies targeting overexpressed surface targets are used. Various antibodies have been developed to recruit ADCC against tumor cells bearing targets such as Her2, CD20, EGFR, and/or CD52. These antibodies bind to the CD16 receptor, which, in turn, is associated with ITAM-containing proteins such as the TCRζ chain–leading to NK cell activation.

Article Snippet: Anderson Cancer Center; National Cancer Institute NK92 cell line modified to express IL-2 and CD16 (haNK) Myelodysplastic syndrome, leukemia, lymphoma, multiple myeloma {"type":"clinical-trial","attrs":{"text":"NCT02742727","term_id":"NCT02742727"}} NCT02742727 PersonGen BioTherapeutics (Suzhou) Co., Ltd.; The First People's Hospital of Hefei; Hefei Binhu Hospital NK92 cell line modified to express anti-CD7 CAR with CD28, 41BB, and TCREζ CD7-positive leukemia and lymphoma {"type":"clinical-trial","attrs":{"text":"NCT02763475","term_id":"NCT02763475"}} NCT02763475 Instituto de Investigatión Hospital Universitario La Paz Cyclophosphamide Fludarabine Haploidentical NK cells IL-2 Acute myeloid leukemia {"type":"clinical-trial","attrs":{"text":"NCT02809092","term_id":"NCT02809092"}} NCT02809092 Hospital de Clinicas de Porto Alegre Haploidentical NK cells Fludarabine Cytarabine granulocyte-colony stimulating factor Acute myeloid leukemia {"type":"clinical-trial","attrs":{"text":"NCT02892695","term_id":"NCT02892695"}} NCT02892695 PersonGen BioTherapeutics (Suzhou) Co., Ltd.; The First People's Hospital of Hefei; Hefei Binhu Hospital NK92 cell line modified to express anti-CD19 CAR with CD28, 41BB, and TCREζ CD19-positive leukemia and lymphoma {"type":"clinical-trial","attrs":{"text":"NCT02944162","term_id":"NCT02944162"}} NCT02944162 PersonGen BioTherapeutics (Suzhou) Co., Ltd.; The First People's Hospital of Hefei; Hefei Binhu Hospital NK92 cell line modified to express anti-CD33 CAR Relapsed/refractory AML {"type":"clinical-trial","attrs":{"text":"NCT02955550","term_id":"NCT02955550"}} NCT02955550 Celularity Incorporated NK cells IL-2 Multiple myeloma {"type":"clinical-trial","attrs":{"text":"NCT03019640","term_id":"NCT03019640"}} NCT03019640 M.D.

Techniques: Activation Assay, Lysis

Journal: Transplantation and cellular therapy

Article Title: NK Cell Adoptive Immunotherapy of Cancer: Evaluating Recognition Strategies and Overcoming Limitations

doi: 10.1016/j.bbmt.2020.09.030

Figure Lengend Snippet: Sample List of Active Trials Involving Allogeneic NK Cells

Article Snippet: Anderson Cancer Center; National Cancer Institute NK92 cell line modified to express IL-2 and CD16 (haNK) Myelodysplastic syndrome, leukemia, lymphoma, multiple myeloma {"type":"clinical-trial","attrs":{"text":"NCT02742727","term_id":"NCT02742727"}} NCT02742727 PersonGen BioTherapeutics (Suzhou) Co., Ltd.; The First People's Hospital of Hefei; Hefei Binhu Hospital NK92 cell line modified to express anti-CD7 CAR with CD28, 41BB, and TCREζ CD7-positive leukemia and lymphoma {"type":"clinical-trial","attrs":{"text":"NCT02763475","term_id":"NCT02763475"}} NCT02763475 Instituto de Investigatión Hospital Universitario La Paz Cyclophosphamide Fludarabine Haploidentical NK cells IL-2 Acute myeloid leukemia {"type":"clinical-trial","attrs":{"text":"NCT02809092","term_id":"NCT02809092"}} NCT02809092 Hospital de Clinicas de Porto Alegre Haploidentical NK cells Fludarabine Cytarabine granulocyte-colony stimulating factor Acute myeloid leukemia {"type":"clinical-trial","attrs":{"text":"NCT02892695","term_id":"NCT02892695"}} NCT02892695 PersonGen BioTherapeutics (Suzhou) Co., Ltd.; The First People's Hospital of Hefei; Hefei Binhu Hospital NK92 cell line modified to express anti-CD19 CAR with CD28, 41BB, and TCREζ CD19-positive leukemia and lymphoma {"type":"clinical-trial","attrs":{"text":"NCT02944162","term_id":"NCT02944162"}} NCT02944162 PersonGen BioTherapeutics (Suzhou) Co., Ltd.; The First People's Hospital of Hefei; Hefei Binhu Hospital NK92 cell line modified to express anti-CD33 CAR Relapsed/refractory AML {"type":"clinical-trial","attrs":{"text":"NCT02955550","term_id":"NCT02955550"}} NCT02955550 Celularity Incorporated NK cells IL-2 Multiple myeloma {"type":"clinical-trial","attrs":{"text":"NCT03019640","term_id":"NCT03019640"}} NCT03019640 M.D.

Techniques: Transplantation Assay, Modification, Transfection, Expressing, Derivative Assay

Journal: Expert review of molecular diagnostics

Article Title: Challenges of Development and Implementation of Point of Care Pharmacogenetic Testing

doi: 10.1080/14737159.2016.1211934

Figure Lengend Snippet: FDA Cleared or Approved PGx Tests (nucleic acid based-tests) (Excerpted from FDA Nucleic Acid based tests on 06/26/16 at (available at http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm330711.htm ) and List of Cleared or Approved Companion Diagnostic Devices (nucleic acid based-tests) (available at http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm ).

Article Snippet: PDGFRB FISH for Gleevec Eligibility in Myelodysplastic Syndrome/Myeloproliferative Disease (MDS/MPD) (ARUP Laboratories, Inc.) , Imatinib , 5q31~33 gene rearrangement.

Techniques: Diagnostic Assay, Luminex, Microarray, Genotyping Assay, Multiplex Assay, Mutagenesis, Amplification

Journal: Molecular and Clinical Oncology

Article Title: Analysis of genes encoding epigenetic regulators in myeloproliferative neoplasms: Coexistence of a novel SETBP1 mutation in a patient with a p.V617F JAK2 positive myelofibrosis

doi: 10.3892/mco.2019.1840

Figure Lengend Snippet: Human cancer cell lines tested.

Article Snippet: Informed consent was obtained from all patients and procedures were approved by the Ethical Committee on Clinical Research of University of Navarra. table ft1 table-wrap mode="anchored" t5 Table II. caption a7 Cell line name Repository (number) Origin A-549 DSMZ (ACC-107) Lung carcinoma BK-006 ECACC p.V617F JAK2 positive PV BK-013 ECACC (98100924) p.V617F JAK2 negative ET BK015 ECACC (99092421) p.V617F JAK2 negative ET DAUDI DSMZ (ACC-78) Burkitt lymphoma EOL-1 DSMZ (ACC-386) Acute myeloid eosinophilic leukemia F-36P DSMZ (ACC-543) Acute myeloid leukemia secondary to myelodysplastic syndrome (MDS) HCC-1937 DSMZ (ACC-513) Breast carcinoma HEL DSMZ ACC-11 Erythroleukemia HL60 DSMZ ACC-3 Acute myeloid leukemia (AML) HU3 Dr Morgan, USA Acute megakaryoblastic leukemia K-562 DSMZ ACC-10 BCR-ABL1 positive chronic myeloid leukemia (CML) in blast crisis KARPAS-299 DSMZ ACC-31 T cell lymphoma KARPAS-422 DSMZ ACC-32 B cell lymphoma M-07e DSMZ ACC-104 Acute megakaryoblastic leukemia MG-63 ATCC: CRL-1427 Osteosarcoma MOLM-13 DSMZ ACC-554 Acute myeloid leukemia (AML) MOLT-16 DSMZ ACC-29 T cell acute lymphoid leukemia (T-ALL) MOLT-4 DSMZ ACC-362 Acute lymphoid leukemia (ALL) MV-411 DSMZ ACC-102 Acute monoblastic/monocytic leukemia RAJI DSMZ ACC-319 Burkitt lymphoma REH DSMZ ACC-22 B-ALL (t(12;21) (p13;q22) (fusion ETV6-RUNX1 )) SET2 DSMZ ACC-608 p.V617F JAK2 positive ET TF-1 DSMZ ACC-334 Erythroleukemia UKE-1 Dr W. Fiedelr, Hamburg, Germany p.V617F JAK2 positive ET transformed to AML Open in a separate window ECACC, European Collection of Cell Culture; DSMZ, Deutsche Sammlung von Mikroorganismen und Zellkulturen.

Techniques: Transformation Assay