NBDC Research ID: hum0116.v2
SUMMARY
Aims: This study aims to bridge the gap between mouse models and human disease. To this end, we identified somatic mutations associated with human acute myelogenous leukemia (AML) pathogenesis using leukemia cells derived from human leukemia stem cells and from patient-derived xenograft (PDX) mice, which recapitulate human disease by transplanting leukemia stem cells into immunodeficient mice. Furthermore, focusing on AML and the development of chimeric antigen receptor (CAR) T-cell therapy, we investigated how enforced expression of the chemokine receptor CXCR4 promotes memory acquisition and long-term persistence of CAR-T cells, thereby enhancing both the therapeutic efficacy and durability against leukemia.
Methods: Target Capture sequencing (Acute Myeloid Leukemia Cancer Panel and 41 genes), single cell RNA sequencing
Participants/Materials: Leukemia stem cells from AML patients or humanized mice with leukemia derived from immune deficiency mice which were infused with human leukemia stem cells, human cord blood-derived CAR-T cells (with or without CXCR4 overexpression) injected into AML patient-derived xenograft (PDX) mice and collected from liver, spleen, and bone marrow, and patient-derived AML blasts
URL: http://www.riken.jp/en/research/labs/ims/hum_dis_model/
| Dataset ID | Type of Data | Criteria | Release Date |
|---|---|---|---|
| JGAS000122 | Controlled-access (Type I) | 2020/11/20 | |
| JGAS000848 | NGS (scRNA-seq) | Controlled-access (Type I) | 2025/12/04 |
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MOLECULAR DATA
Target Capture: AML cancer panel
| Participants/Materials |
AML (ICD10: C920): 19 cases Leukemia stem cell: 33 samples, Pre-leukemia stem cell: 2 samples, T-cell: 6 samples, B-cell: 2 samples (total 43 samples) 37 human leukemia stem cell samples from 37 humanized mice with leukemia derived from immune deficiency mice which were infused with human leukemia stem cell from 12 patients with AML |
| Targets | Target Capture |
| Target Loci for Capture Methods | xGen® Acute Myeloid Leukemia Cancer Panel |
| Platform | Illumina [HiSeq 1500] |
| Library Source |
DNAs extracted from leukemia stem cells, pre-leukemia stem cells, T-cell and B-cells DNAs extracted from leukemia stem cells from humanized mice with leukemia derived from immune deficiency mice which were infused with human leukemia stem cells |
| Cell Lines | - |
| Library Construction (kit name) |
KAPA Hyper Prep kit xGen@ Acute Myeloid Leukemia Cancer Panel |
| Fragmentation Methods | - |
| Spot Type | Single-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 50 bp |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000133 |
| Total Data Volume | 423 GB (fastq) |
| Comments (Policies) | NBDC policy |
| Participants/Materials |
AML (ICD10: C920): 106 cases 1) peripheral blood: 45 samples 2) bone marrow aspirate: 19 samples 3) human leukemia cells from spleen of humanized mice with leukemia derived from immune deficiency mice which were infused with peripheral blood, bone marrow aspirate or samples from patients with AML: 6 samples 4) human leukemia cells from bone marrow aspirate of humanized mice with leukemia derived from immune deficiency mice which were infused with peripheral blood, bone marrow aspirate or samples from patients with AML: 36 samples |
| Targets | Target Capture |
| Target Loci for Capture Methods | Coding region of 41 genes (NRAS, KRAS, FLT3, TP53, NPM1, KIT, IDH1, IDH2, SF3B1, U2AF1, TET2, DNMT3A, ASXL1, ASXL2, BCOR, RUNX1, KMT2A(MLL), WT1(WT-1), GATA2, STAG2, RAD21, SMC1A, SMC3, MPL, NF1, PTPN11, CSF3R, CBL, CEBPA, SRSF2, DHX15, ZRSR2, EZH2, SETBP1, KDM6A, ETV6, CUX1, PHF6, MGA, ZBTB7A, PPM1D) |
| Platform | Illumina [HiSeq 2500] |
| Library Source |
DNAs extracted from peripheral blood and bone marrow aspirate DNAs extracted from human leukemia cells from spleen and bone marrow aspirate of humanized mice with leukemia derived from immune deficiency mice which were infused with peripheral blood, bone marrow aspirate or samples from patients with AML |
| Cell Lines | - |
| Library Construction (kit name) | multiplex PCR + 2nd PCR |
| Fragmentation Methods | - |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 151 bp |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000355 |
| Total Data Volume | 23 GB (fastq) |
| Comments (Policies) | NBDC policy |
| Participants/Materials |
AML (ICD10: C920): 1 case human cord blood–derived CAR-T cells (with or without CXCR4 overexpression) derived from 5 healthy donors: 12 samples patient-derived AML blasts: 6 samples |
| Targets | scRNA-seq |
| Target Loci for Capture Methods | - |
| Platform | Illumina [NovaSeq 6000] |
| Library Source | RNAs extracted from CAR-T cells and patient-derived AML blasts |
| Cell Lines | - |
| Library Construction (kit name) | Chromium Next GEM Single Cell 5' Kit v2 |
| Fragmentation Methods | included in the above library construction kit |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 150 bp |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000990 |
| Total Data Volume | 1.2 TB (fastq) |
| Comments (Policies) | NBDC policy |
DATA PROVIDER
Principal Investigator: Fumihiko Ishikawa
Affiliation: Laboratory for Human Disease Models, Riken Center for Integrative Medical Sciences
Project / Group Name: Target AML project
Funds / Grants (Research Project Number):
| Name | Title | Project Number |
|---|---|---|
PUBLICATIONS
| Title | DOI | Dataset ID | |
|---|---|---|---|
| 1 | Overcoming mutational complexity in acute myeloid leukemia by inhibition of critical pathways | doi: 10.1126/scitranslmed.aao1214 | JGAD000133 |
| 2 | Combined inhibition of XIAP and BCL2 drives maximal therapeutic efficacy in genetically diverse aggressive Acute Myeloid Leukemia | doi: 10.1038/s43018-021-00177-w | JGAD000355 |
USRES (Controlled-access Data)
| Principal Investigator | Affiliation | Country/Region | Research Title | Data in Use (Dataset ID) | Period of Data Use |
|---|---|---|---|---|---|
