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Combined Functional and Genomic Single clonal Stem Cell Analysis Pinpointed at Diagnosis Leukemic Clones Responsible for Acute Myeloid Leukemia Relapse

ABSTRACT: Acute myeloid leukemia (AML) is a hematological malignancy, associated with unfavorable patient outcome primarily due to disease relapse. Since specific early leukemic hematopoietic stem and progenitor cells (HSPCs) are suggested to be responsible for AML propagation, the present study used single cell analysis (SCA) to detect and explore rare relapse-initiating HSPC clones, appearing already at diagnosis. To address inherent SCA limitations, we developed a unique high-resolution technique capable to follow single cell-derived subclones of heterogeneous HSPC subpopulations during AML evolution. Each of these subclones was evaluated for chemo-resistance, in-vivo leukemogenic potential, mutational profile, and the subclone cell of origin identified using reconstruction of phylogenetic trees. This study, employing combined functional and genomic analyses, unraveled the patient-specific HSPC subpopulations involved in chemo-resistance and determined, at time of diagnosis, the phenotype of the relapse-initiating clone, allowing early prediction of AML recurrence and suggesting novel precise therapeutic targets for relapse prevention.

INSTRUMENT(S): NextSeq 550

ORGANISM(S): Homo sapiens

SUBMITTER: Noa Chapal Ilani

PROVIDER: E-MTAB-12238 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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