Effect of CX-4945 on OCI and HL-60 Acute Myeloid Leukemia cell lines
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q-Exactive HF
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Vladimir Besada
PROVIDER: MSV000095299 | MassIVE | Thu Jul 11 05:48:00 BST 2024
REPOSITORIES: MassIVE
Similar Datasets
Project description:Relative quantification of phosphoproteome modulated by CK2 inhibitor CIGB-300 [40 uM] after 30 min treatment for two leukemia cell lines. Protein extracts were processed by FASP procedure. File names labeled with letters L and T for Lys-C and Trypsin derived digestions, respectively. Labeled P for enriched phosphopeptides via TiO2.
2024-07-11 | MSV000095306 | MassIVE
Project description:Treatment of acute myeloid leukemia (AML) has changed over the last few years, after the discovery of new drugs selectively targeting AML blasts. Although 3/7 remains the standard of care for most AML patients, several new targeted agents (such as FLT3 inhibitors, CPX-351, gemtuzumab ozogamicin, BCL-2 inhibitor, and oral azacitidine), either as single agents or combined with standard chemotherapy, are approaching clinical practice, starting a new era in AML management. Moreover, emerging evidence has demonstrated that high-risk AML patients might benefit from both allogeneic stem cell transplant and maintenance therapy, providing new opportunities, as well as new challenges, for treating clinicians. In this review, we summarize available data on first-line therapy in young AML patients focusing on targeted therapies, integrating established practice with new evidence, in the effort to outline the contours of a new therapeutic paradigm, that of a "total therapy", which goes beyond obtaining complete remission.
| S-EPMC9581198 | biostudies-literature
Project description:Differentiation therapy has been successfully applied clinically in cases of acute promyelocytic leukemia (APL), but few differentiation-induction agents other than all-trans retinoic acid (ATRA) have been discovered clinically. Based on our previously reported neuritogenic differentiation activity of synthetic dimeric derivatives of securinine, we explored the leukemia differentiation-induction activity of such as compound, SN3-L6. It was found that SN3-L6 induces transdifferentiation of both acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML) cells but unexpectedly, a new transdifferentiation pathway from APL cells to morphologically and immunologically normal megakaryocytes and platelets were discovered. SN3-L6 fails to induce transdifferentiation of ATRA-produced mature granulocytes into megakaryocytes, indicating its selectivity between mature and immature cells. SN3-L6 induces CML K562 cells to transdifferentiate into apoptotic megakaryocytes but without platelet formation, indicating a desirable selectivity between different leukemia cells. Our data illuminate a differentiation gap between AML cells and platelets, and promises applications in leukemia differentiation therapy strategy.
| S-EPMC7665178 | biostudies-literature
Project description:The nitric oxide (NO) prodrug JS-K is shown to have anticancer activity. To profile the molecular events associated with the anticancer effects of JS-K, HL-60 leukemia cells were treated with JS-K and subjected to microarray and real-time RT-PCR analysis. JS-K induced concentration- and time-dependent gene expression changes in HL-60 cells corresponding to the cytolethality effects. The apoptotic genes (caspases, Bax, and TNF-alpha) were induced, and differentiation-related genes (CD14, ITGAM, and VIM) were increased. For acute phase protein genes, some were increased (TP53, JUN) while others were suppressed (c-myc, cyclin E). The expression of anti-angiogenesis genes THBS1 and CD36 and genes involved in tumor cell migration such as tissue inhibitors of metalloproteinases, were also increased by JS-K. Confocal analysis confirmed key gene changes at the protein levels. Thus, multiple molecular events are associated with JS-K effects in killing HL-60, which could be molecular targets for this novel anticancer NO prodrug.
| S-EPMC3496159 | biostudies-literature
Project description:Clofarabine has shown activity and tolerability in older patients with acute myeloid leukemia (AML). We investigated the safety and tolerability of an oral formulation of clofarabine for consolidation therapy of patients aged 60 and older with AML. In this phase I study, twenty-two patients older than 60 years with AML in first complete remission were treated once daily with oral clofarabine for 14 or 21 days of a 28-day cycle, for up to five cycles. Dose escalation from 1 mg to 6 mg daily using a 3?+?3 design was used to determine dose-limiting toxicities (DLT), the maximum tolerated dose (MTD), and tolerability of oral clofarabine. No DLTs or Grade 3-4 nonhematologic toxicities were observed. The primary toxicities were hematologic, including uncomplicated grade 3-4 neutropenia (50%) and thrombocytopenia (50%). Given that myelosuppression necessitating dose delays/reductions was observed more commonly at higher doses, the recommended phase II dose is 2 mg daily for 21 of 28 days. At doses equal to or greater than 2 mg, the median relapse-free survival was 28.35 months. Oral clofarabine was well-tolerated with encouraging activity in patients older than 60 years. Further investigation of oral clofarabine as a consolidation and/or maintenance therapy in AML for older individuals is warranted. (ClinicalTrials.gov:NCT00727766).
| S-EPMC4378713 | biostudies-literature
Project description:Older patients with acute myeloid leukemia (AML) have poor outcomes with standard induction chemotherapy. We retrospectively reviewed our institute's experience with epigenetic (Epi) versus cytarabine- and anthracycline-based intensive chemotherapy (IC) as induction in newly diagnosed AML patients aged 60 years and older. One hundred sixty-seven patients (n = 84, IC; n = 83, Epi) were assessed; 69 patients received decitabine and 14 azacitidine. Baseline characteristics between the IC and Epi patient cohorts were not statistically different except for age, initial white blood cell count, and comorbidity index. Overall response rate (ORR, 50% vs. 28%, respectively, P < 0.01) and complete response rate (CRR, 43% vs. 20%, respectively, P < 0.01) were superior following IC vs. Epi. Although univariate analysis demonstrated longer overall survival after IC (10.7 vs. 9.1 months, P = 0.012), multivariate analysis showed no independent impact of induction treatment. Treatment-related mortality was not statistically different in the two groups. Outcomes of patients with secondary, poor cytogenetic risk, FLT-3 mutated AML, or relapsed/refractory disease after IC or Epi were not significantly different. Outcomes of patients receiving IC versus a 10-day decitabine regimen (n = 63) also were not significantly different. Our results suggest that IC and Epi therapy are clinically equivalent approaches for upfront treatment of older patients with AML and that other factors (feasibility, toxicity, cost, etc.) should drive treatment decisions. Prospective randomized trials to determine the optimal induction approach for specific patient subsets are needed.
| S-EPMC6791130 | biostudies-literature
Project description:Cancer-derived iPSCs have provided valuable insight into oncogenesis, but human cancer cells can often be difficult to reprogram, especially in cases of complex genetic abnormalities. Here we report, to our knowledge, the first successful generation of an iPSC line from a human immortalized acute myeloid leukemia (AML) cell line, the cell line HL-60. This iPSC line retains a majority of the leukemic genotype and displays defects in myeloid differentiation, thus providing a tool for modeling and studying AML.
| S-EPMC8031422 | biostudies-literature
Project description:Clofarabine is a second generation nucleoside analogue with activity in adults with acute myeloid leukemia (AML). A phase I trial of clofarabine, idarubicin, and cytarabine (CIA) in relapsed and refractory AML had shown an overall response rate (ORR) of 48%. To explore this combination further, we conducted a phase II study of (CIA) in patients with newly diagnosed AML ?60 years. Patients ?18-60 years with AML and adequate organ function were enrolled. Induction therapy consisted of clofarabine (C) 20 mg m?² IV daily (days 1-5), idarubicin (I) 10 mg m?² IV daily (days 1-3), and cytarabine (A) 1 g m?² IV daily (days 1-5). Patients in remission received up to six consolidation cycles (C 15 mg m?² × 3, I 8 mg m?² × 2, and A 0.75 g m?² × 3). Fifty-seven patients were evaluable. ORR was 79%. With a median follow up of 10.9 months, the median overall survival (OS) was not reached, the median event-free survival (EFS) was 13.5 months. Most toxicities were ?grade 2. Four week mortality was 2%. In subgroup analysis, patients ?40 years had better OS (P?=?0.04) and EFS (P?=?0.04) compared to patients >40 years. Compared to historical patients treated with idarubicin and cyarabine (IA), the OS and EFS were significantly longer for CIA treated patients. In multivariate analysis, CIA retained its favorable impact on OS compared to IA. Thus, CIA is an effective and safe therapy for patients ?60 years with newly diagnosed AML.
| S-EPMC4110914 | biostudies-literature
Project description:A recent phase 3 trial showed that outcome of older patients with secondary acute myeloid leukemia (AML) may be improved by a liposomal encapsulation of cytarabine and daunorubicin (CPX-351). This phase 3 study represents a unique example of prospective data in this rare subgroup providing basis for comparison with real life data. Here, we retrospectively assessed characteristics and outcome of patients aged 60-75 years with secondary or therapy-related AML in real life. Out of 218 patients that fulfilled CPX-351 study criteria, 181 patients (83.0%) received antileukemic treatment either intensive chemotherapy (n = 121) or hypomethylating agents (HMA, n = 60). As compared with patients treated by chemotherapy, HMA-treated patients were older, had lower WBC, more often AML with antecedent myelodysplastic syndrome and adverse cytogenetic risk. In chemotherapy-treated patients, the complete response rate was 69%, median overall survival (OS) was 11 months whereas 3-year and 5-year OS was 21% and 17%, respectively. In HMA-treated patients, the complete response rate was 15%, median OS was 11 months whereas 3-year and 5-year OS was 15% and 2%, respectively. In conclusion, although outcome of older patients with high-risk AML is very poor, a significant proportion of patients treated by standard intensive chemotherapy but not HMA are long-term survivors.
| S-EPMC6639188 | biostudies-literature
Project description:To investigate the transcriptomic effects upon loss of CSNK2A1 (Casein kinase 2, CK2), MLL and SGF29 in the AML cell line U937 we performed CRISPR knockouts, as well as transduction with non-targeting controls, and harvested samples for bulk RNA-Seq. We then performed gene expression profiling analysis using data obtained from RNA-seq of the different CRISPRko perturbations compared to non-targeting controls.
2023-11-10 | GSE217776 | GEO