A5044229710- Acute Myeloid Leukemia Research
- CAR-T cell therapy research
- Chronic Myeloid Leukemia Treatments
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Gene expression and cancer classification
- Immune cells in cancer
- Molecular Biology Techniques and Applications
- Multiple Myeloma Research and Treatments
- Chronic Lymphocytic Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Acute Lymphoblastic Leukemia research
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Immune Cell Function and Interaction
- Platelet Disorders and Treatments
- Ubiquitin and proteasome pathways
- Cancer Mechanisms and Therapy
- Bone health and treatments
- Hematopoietic Stem Cell Transplantation
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Advanced biosensing and bioanalysis techniques
- Ethics in Clinical Research
The University of Texas MD Anderson Cancer Center
2013-2024
Leukemia and Lymphoma Society
2023
Leukemia Research Foundation
2022
University of the Ryukyus
2004
University of Michigan
2004
Abstract Clonal diversity is a consequence of cancer cell evolution driven by Darwinian selection. Precise characterization clonal architecture essential to understand the evolutionary history tumor development and its association with treatment resistance. Here, using single-cell DNA sequencing, we report mutational histories 123 acute myeloid leukemia (AML) patients. The data reveals cell-level mutation co-occurrence enables reconstruction characterized linear branching patterns evolution,...
To enable the characterization of genetic heterogeneity in tumor cell populations, we developed a novel microfluidic approach that barcodes amplified genomic DNA from thousands individual cancer cells confined to droplets. The are then used reassemble profiles next-generation sequencing data. By using this approach, sequenced longitudinally collected acute myeloid leukemia (AML) populations two patients and genotyped up 62 disease relevant loci across more than 16,000 cells. Targeted...
Measurable residual disease (MRD) is highly prognostic for relapse and overall survival (OS) in acute lymphoblastic leukemia (ALL), although many patients with apparent "MRD negativity" by standard assays still relapse. We evaluated the clinical impact of a sensitive next-generation sequencing (NGS) MRD assay 74 adults ALL undergoing frontline therapy. Among remission samples that were negative multiparameter flow cytometry (MFC), 46% MRD+ NGS assay. After 1 cycle induction chemotherapy,...
PURPOSE Azacitidine plus venetoclax is a standard of care for patients with newly diagnosed AML who are unfit intensive chemotherapy. However, FLT3 mutations common mechanism resistance to this regimen. The addition gilteritinib, an oral inhibitor, azacitidine and may improve outcomes in FLT3-mutated AML. METHODS This phase I/II study evaluated azacitidine, venetoclax, gilteritinib two cohorts: (1) were chemotherapy or (2) relapsed/refractory (ClinicalTrials.gov identifier: NCT04140487 )....
Abstract Interferon gamma (IFNγ) is a critical cytokine known for its diverse roles in immune regulation, inflammation, and tumor surveillance. However, while IFNγ levels were elevated sera of most newly diagnosed acute myeloid leukemia (AML) patients, complex interplay AML remains insufficiently understood. We aim to characterize these interactions through comprehensive bulk single-cell approaches bone marrow patients. identify monocytic as having unique microenvironment characterized by...
Acute promyelocytic leukemia (APL) is a subtype of myeloid characterized by differentiation block at the promyelocyte stage. Besides presence chromosomal rearrangement t(15;17), leading to formation PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis primary and relapse APL identify somatic alterations, which cooperate with pathogenesis We explored landscape...
Abstract Allosteric inhibitors of mutant IDH1 or IDH2 induce terminal differentiation the leukemic blasts and provide durable clinical responses in approximately 40% acute myeloid leukemia (AML) patients with mutations. However, primary resistance acquired to drugs are major issues. To understand molecular underpinnings IDH (IDHi), we perform multipronged genomic analyses (DNA sequencing, RNA sequencing cytosine methylation profiling) longitudinally collected specimens from 60 IDH1-...
Reverse transcription polymerase chain reaction (RT-PCR) for BCR::ABL1 is the most common and widely accepted method of measurable residual disease (MRD) assessment in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL); however, RT-PCR may not be an optimal measure MRD many cases Ph+ ALL. We evaluated clinical impact a highly sensitive next-generation sequencing (NGS) assay (sensitivity 10-6 ) its correlation with patients Overall, 32% had discordance between by NGS, 31%...
Although TRIzol is widely used for preservation and isolation of RNA, there suspicion that prolonged sample storage in may affect array-based gene expression profiling (GEP) through premature termination during reverse transcription.GEP on Illumina arrays compared paired aliquots (cryopreserved or stored TRIzol) primary samples multiple myeloma (MM) acute myeloid leukemia (AML). Data were analyzed at the "probe level" (a single consensus value) "bead (multiple measurements provided by...
Abstract Circulating cell-free DNA (ccfDNA) allows for noninvasive peripheral blood sampling of cancer-associated mutations and has established clinical utility in several solid tumors. We performed targeted next-generation sequencing ccfDNA bone marrow at the time diagnosis after achieving remission 22 patients with acute myeloid leukemia (AML). Among 28 genes sequenced by both platforms, a total 39 unique somatic were detected. Five (13%) detected only ccfDNA, 15 (38%) marrow. 19 sources,...
Acute myeloid leukemia (AML) remains a difficult disease to treat disease. In phase 2 clinical trial in patients with relapsed/refractory AML, combining the hypomethylating agent, azacitidine, PD-1 checkpoint inhibitor, nivolumab, demonstrated encouraging response rates (33%), median event-free, and overall survival, compared historical cohort of contemporary treated azacitidine-based therapies, an acceptable safety profile. Biomarkers are yet be determined. this study, we leveraged...
Acute myeloid leukemia (AML) is a heterogeneous malignancy of the blood primarily treated with intensive chemotherapy. The allogeneic T-cell antileukemic activity via donor lymphocyte infusions and stem cell transplantation suggests potential role for checkpoint blockade therapy in AML. While clinical trials employing these treatments have fallen short expected results, deeper exploration into functional states T cells AML could bridge this knowledge gap. In study, we analyzed polyfunctional...
Summary One of the pervasive features cancer is diversity mutations found in malignant cells within same tumor; a phenomenon called clonal or intratumor heterogeneity. Clonal allows tumors to adapt selective pressure treatment and likely contributes development resistance recurrence. Thus, ability precisely delineate substructure tumor, including evolutionary history its co-occurrence mutations, necessary understand overcome resistance. However, DNA sequencing bulk tumor samples cannot...
Approximately 20-50% patients with chronic phase myeloid leukemia (CML-CP) treated tyrosine kinase inhibitors (TKIs) or myelofibrosis (MF) ruxolitinib develop grade ≥3 thrombocytopenia needing treatment interruptions and dose reductions. We conducted a non-randomized, II, single-arm study to determine the efficacy of eltrombopag for CML MF persistent while on TKI ruxolitinib. Eltrombopag was initiated at 50 mg/day, escalation up 300 mg daily allowed every 2 weeks. Twenty-one were enrolled...
Children with chronic myeloid leukemia (CML) tend to present higher white blood counts and larger spleens than adults CML, suggesting that the biology of pediatric adult CML may differ. To investigate whether have unique molecular characteristics, we studied transcriptomic signature CD34+ cells healthy control cells. Using high-throughput RNA sequencing, found 567 genes (207 up- 360 downregulated) differentially expressed in compared Directly comparing cells, 398 (258 140 downregulated),...
Abstract Background A recent breakthrough therapy combining the BCL‐2 inhibitor venetoclax with hypomethylating agents (HMAs) targeting DNA methyltransferase has improved outcomes for patients acute myeloid leukemia (AML), but responses and long‐term survival in older/unfit relapsed/refractory AML remain suboptimal. Recent studies showed that inhibition of or modulates T‐cell immunity. Methods By using flow cytometry time‐of‐flight mass cytometry, authors examined effects HMA decitabine...