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2,470 results for “Acute Myeloid Leukemia”
First in Human Testing of Dose-escalation of SAR440234 in Patients With Acute Myeloid Leukemia, Acute Lymphoid Leukemia and Myelodysplastic Syndrome
ClinicalTrials.gov study NCT03594955. IPD Sharing: YES. Countries: 2. Publications: 1.
Data from: Age-specific induction of mutant p53 drives clonal hematopoiesis and acute myeloid leukemia in adult mice
<p>The investigation of the mechanisms behind p53 mutations in acute myeloid leukemia (AML) has been limited by the lack of suitable mouse models, which historically have resulted in lymphoma rather than leukemia. This study introduces two new AML mouse models. One model induces mutant p53 and <em>Mdm2</em> haploinsufficiency in early development, showing the role of Mdm2 in myeloid-biased hematopoiesis and AML predisposition, independent of p53. The second model mimics clonal hematopoiesis by inducing mutant p53 in adult hematopoietic stem cells, demonstrating that the timing of p53 mutation determines AML versus lymphoma development. In this context, age-related changes in hematopoietic stem cells (HSCs), collaborates with mutant p53 to predispose towards myeloid transformation rather than lymphoma development. Our study unveils new insights into the cooperative impact of HSC age, <em>Trp53</em> mutations and <em>Mdm2</em> haploinsufficiency on clonal hematopoiesis and the development of myeloid malignancies.</p>
HERV-K (HML-2) insertion polymorphisms in the 8q24.13 region and their potential etiological associations with acute myeloid leukemia
<p>Human endogenous retroviruses (HERVs) are LTR retrotransposons that are present in the human genome. Among them, members of the HERV-K (HML-2) group are suspected to play a role in the development of different types of cancer, including lung, ovarian, and prostate cancer, as well as leukemia. Acute myeloid leukemia (AML) is an important disease that causes 1% of cancer deaths in the United States and has a survival rate of 28.7%. Here, we describe a method for assessing the statistical association between HERV-K (HML-2) transposable element insertion polymorphisms (or TIPs) and AML, using whole-genome sequencing and read mapping using TIP_finder software. Our results suggest that 101 polymorphisms involving HERV-K (HML-2) elements were correlated with AML, with a percentage between 44.4 to 56.6%, most of which (70) were located in the region from 8q24.13 to 8q24.21. Moreover, it was found that the TRIB1, LRATD2, POU5F1B, MYC, PCAT1, PVT1, and CCDC26 genes could be displaced or fragmented by TIPs. Furthermore, a general method was devised to facilitate analysis of the correlation between transposable element insertions and specific diseases. Finally, although the relationship between HERV-K (HML-2) TIPs and AML remains unclear, the data reported in this study indicate a statistical correlation, as supported by the χ2 test with p-values < 0.05.</p>
Framework of clonal mutations concurrent with WT1 mutations in adults with acute myeloid leukemia (Alliance)
<p>Mutations affecting the tumor suppressor gene, WT1 transcription factor (<em>WT1</em>) are relatively common in adults with acute myeloid leukemia (AML) and have been reported to associate with a poor prognosis. However, there is limited data describing additional mutations co-occurring with <em>WT1</em> as well as clonal architecture and complexity. We performed targeted DNA sequencing on 96 pretreatment samples from adult patients with <em>de novo</em> AML who harbored <em>WT1</em> mutations and subsequently performed single-cell DNA sequencing on a subset of these samples. <em>FLT3</em>-ITD mutations were the most common co-occurring mutations detected in 47% of <em>WT1</em>-mutated patients (<em>WT1<sup>mut</sup></em>/<em>FLT3</em>-ITD). Among <em>WT1<sup>mut</sup></em>/<em>FLT3</em>-ITD patients, <em>NPM1</em> mutations were observed in 58% of patients. In contrast, patients with <em>WT1</em>-mutated AML but no <em>FLT3</em>-ITD (<em>WT1<sup>mut</sup></em>/no <em>FLT3</em>-ITD) had significantly more frequent mutations in alternative signal activating pathways (<em>FLT3</em>-TKD: 25% vs 11%; and NRAS: 37% vs 11%) compared with <em>WT1<sup>mut</sup></em>/<em>FLT3</em>-ITD patients, and, notably, fewer mutations in <em>NPM1</em> (16% vs 58%). Given the difference in NRAS mutation frequency in <em>WT1<sup>mut</sup></em>/<em>FLT3</em>-ITD compared to <em>WT1<sup>mut</sup></em>/no <em>FLT3</em>-ITD patients, we then compared the variant allele frequencies (VAF) of <em>NRAS</em> mutations in the presence or absence of FLT3 mutations. There was a trend for higher NRAS VAF in <em>WT1</em>-mutated patients with concurrent <em>NRAS</em> mutations but no <em>FLT3</em> mutations (<em>FLT3</em>-WT), suggesting this may be due to WT1 being the founding mutation with two or more distinct sub-clones. To further delineate this observation, we performed single-cell DNA sequencing on seven samples with co-occurring <em>WT1</em> and <em>NRAS</em> mutations with or without <em>FLT3</em> mutations. Single-cell sequencing revealed that <em>WT1</em> mutations were more frequently observed in the founder clone (6 out of 7 samples), with or without <em>NPM1</em> mutations. Five of the seven samples included in the single-cell sequencing harbored both a <em>FLT3</em> (ITD or TKD) and an <em>NRAS</em> mutation. The analysis shows these mutations arose in mutually exclusive sub-clones from a <em>WT1</em> mutated founder clone in all 5 cases. These data, to our knowledge, represent the largest series of adults with <em>WT1</em>-mutated AML, and for the first time describe clonal architecture and the combination of mutations co-occurring in single cells. These data provide a deeper understanding of the genomic complexity and biology of <em>WT1</em>-mutated AML and may provide insight into the future development of novel therapeutic strategies.</p>
Genomic Predictors of Decitabine Response in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes
ClinicalTrials.gov study NCT01687400. IPD Sharing: NO. Countries: 1. Publications: 1.
AMD3100 Plus Mitoxantrone, Etoposide and Cytarabine in Acute Myeloid Leukemia
ClinicalTrials.gov study NCT00512252. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
ClinicalTrials.gov study NCT00742625. IPD Sharing: Not stated. Countries: 1. Publications: 2.
MEN1703 (SEL24) in Participants With Acute Myeloid Leukemia
ClinicalTrials.gov study NCT03008187. IPD Sharing: NO. Countries: 4. Publications: 1.
Use of Ribavirin and Low Dose Ara-C to Treat Acute Myeloid Leukemia
ClinicalTrials.gov study NCT01056523. IPD Sharing: Not stated. Countries: 1. Publications: 2.
Vaccine Therapy and GM-CSF in Treating Patients With Acute Myeloid Leukemia, Myelodysplastic Syndromes, Non-Small Cell Lung Cancer, or Mesothelioma
ClinicalTrials.gov study NCT00398138. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Decitabine and Midostaurin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
ClinicalTrials.gov study NCT01846624. IPD Sharing: Not stated. Countries: 1. Publications: 1.
A Patient-Centered Communication Tool (UR-GOAL) Versus Usual Care for Older Patients With Acute Myeloid Leukemia, Their Caregivers, and Their Oncologists
ClinicalTrials.gov study NCT05335369. IPD Sharing: YES. Countries: 1. Publications: 3.
Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia
ClinicalTrials.gov study NCT01420926. IPD Sharing: Not stated. Countries: 1. Publications: 3.
Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome
ClinicalTrials.gov study NCT02521493. IPD Sharing: Not stated. Countries: 6. Publications: 1.
Cytokine-induced Memory-like NK Cells in Patients With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)
ClinicalTrials.gov study NCT01898793. IPD Sharing: NO. Countries: 1. Publications: 4.
Phase II Study of Decitabine and Cytarabine for Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
ClinicalTrials.gov study NCT01829503. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Isavuconazole in Preventing Invasive Fungal Infections in Adult Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome and Neutropenia
ClinicalTrials.gov study NCT03019939. IPD Sharing: Not stated. Countries: 1. Publications: 2.
A Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia.
ClinicalTrials.gov study NCT02310321. IPD Sharing: YES. Countries: 3. Publications: 0.
A Dose-finding Study of CC-90009 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher-risk Myelodysplastic Syndromes
ClinicalTrials.gov study NCT02848001. IPD Sharing: Not stated. Countries: 6. Publications: 1.
Lenalidomide in Older Patients With Acute Myeloid Leukemia Without Chromosome 5q Abnormalities
ClinicalTrials.gov study NCT00546897. IPD Sharing: Not stated. Countries: 1. Publications: 4.
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DANDI Archive for NWB datasets
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International Brain Laboratory public data
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OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.