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A Cultured Leukemia Stem Cell Model Enables Validation of CDK6 as a Stemness Target Against Acute Myeloid Leukemia

Acute myeloid leukemia (AML) represents a group of aggressive hematological malignancies, the clinical management of which is made challenging due to the persistence of rare and therapy resistant leukemia stem cells (LSCs) which serve as a source of disease relapse and poor outcomes. There are currently a paucity of methods to reliably enrich and study LSCs, hindering the development of therapies that specifically target LSCs. In this study, we deeply characterize the OCI-AML8227 culture model, which maintains a functional stemness hierarchy originating from its highly primitive CD34⁺CD38⁻ cells, to elucidate LSC biology and uncover LSC-specific therapeutic vulnerabilities. We analyzed both bulk and single-cell proteomics, transcriptomics, and epigenomics to generate a LSC protein-protein interaction network, which was then integrated with an LSC-focused small molecule screen using this model. From these findings, CDK6 was discovered as a therapeutic vulnerability specific to LSCs, which was validated in findings from the BEAT-AML cohort and a patient-derived xenograft (PDX) panel of AML samples through palbociclib treatment. Taken together, our studies validate CDK6 as a druggable vulnerability in LSCs, and authenticate OCI-AML8227 cells as a LSC target discovery engine.

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Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS50000000786 RNASeq
EGAS50000000787 Epigenetics
EGAS50000000788 Epigenetics
EGAS50000000789 RNASeq

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF50000277486 fastq.gz 3.7 GB
EGAF50000277487 fastq.gz 3.7 GB
EGAF50000277488 fastq.gz 3.8 GB
EGAF50000277489 fastq.gz 3.4 GB
EGAF50000277490 fastq.gz 3.0 GB
EGAF50000277491 fastq.gz 2.5 GB
EGAF50000277492 fastq.gz 3.8 GB
EGAF50000277493 fastq.gz 3.9 GB
EGAF50000277494 fastq.gz 3.3 GB
EGAF50000277495 fastq.gz 3.4 GB
EGAF50000277496 fastq.gz 3.1 GB
EGAF50000277497 fastq.gz 3.2 GB
EGAF50000277498 fastq.gz 3.6 GB
EGAF50000277499 fastq.gz 3.5 GB
EGAF50000277500 fastq.gz 2.6 GB
EGAF50000277501 fastq.gz 2.6 GB
EGAF50000277502 fastq.gz 2.7 GB
EGAF50000277503 fastq.gz 3.4 GB
EGAF50000277504 fastq.gz 3.6 GB
EGAF50000277505 fastq.gz 3.8 GB
EGAF50000277506 fastq.gz 3.7 GB
EGAF50000277507 fastq.gz 3.7 GB
EGAF50000277508 fastq.gz 3.5 GB
EGAF50000277509 fastq.gz 3.6 GB
EGAF50000277510 fastq.gz 2.9 GB
EGAF50000277511 fastq.gz 3.0 GB
EGAF50000277512 fastq.gz 3.2 GB
EGAF50000277513 fastq.gz 3.3 GB
EGAF50000277514 fastq.gz 3.5 GB
EGAF50000277515 fastq.gz 3.6 GB
EGAF50000277516 fastq.gz 3.4 GB
EGAF50000277517 fastq.gz 2.3 GB
EGAF50000277518 fastq.gz 3.1 GB
EGAF50000277519 fastq.gz 3.3 GB
EGAF50000277520 fastq.gz 848.9 MB
EGAF50000277521 fastq.gz 2.4 GB
EGAF50000277522 fastq.gz 5.3 GB
EGAF50000277523 fastq.gz 793.7 MB
EGAF50000277524 fastq.gz 276.0 MB
EGAF50000277525 fastq.gz 297.9 MB
EGAF50000277526 fastq.gz 846.2 MB
EGAF50000277527 fastq.gz 1.8 GB
EGAF50000277528 fastq.gz 3.6 GB
EGAF50000277529 fastq.gz 3.7 GB
EGAF50000277530 fastq.gz 302.0 MB
EGAF50000277531 fastq.gz 856.8 MB
EGAF50000277532 fastq.gz 1.9 GB
EGAF50000277533 fastq.gz 281.2 MB
EGAF50000277534 fastq.gz 1.2 GB
EGAF50000277535 fastq.gz 2.3 GB
EGAF50000277536 fastq.gz 2.3 GB
EGAF50000277537 fastq.gz 534.6 MB
EGAF50000277538 fastq.gz 1.1 GB
EGAF50000277539 fastq.gz 2.1 GB
EGAF50000277540 fastq.gz 507.0 MB
EGAF50000277541 fastq.gz 2.1 GB
EGAF50000277542 fastq.gz 2.1 GB
EGAF50000277543 fastq.gz 506.0 MB
EGAF50000277544 fastq.gz 1.1 GB
EGAF50000277545 fastq.gz 2.1 GB
60 Files (154.0 GB)