Cellular Reprogramming Allows Generation of Autologous Hematopoietic Progenitors From AML Patients That Are Devoid of Patient-Specific Genomic Aberrations

Stem Cells
Kyle R SalciMickie Bhatia

Abstract

Current treatments that use hematopoietic progenitor cell (HPC) transplantation in acute myeloid leukemia (AML) patients substantially reduce the risk of relapse, but are limited by the availability of immune compatible healthy HPCs. Although cellular reprogramming has the potential to provide a novel autologous source of HPCs for transplantation, the applicability of this technology toward the derivation of healthy autologous hematopoietic cells devoid of patient-specific leukemic aberrations from AML patients must first be evaluated. Here, we report the generation of human AML patient-specific hematopoietic progenitors that are capable of normal in vitro differentiation to myeloid lineages and are devoid of leukemia-associated aberration found in matched patient bone marrow. Skin fibroblasts were obtained from AML patients whose leukemic cells possessed a distinct, leukemia-associated aberration, and used to create AML patient-specific induced pluripotent stem cells (iPSCs). Through hematopoietic differentiation of AML patient iPSCs, coupled with cytogenetic interrogation, we reveal that AML patient-specific HPCs possess normal progenitor capacity and are devoid of leukemia-associated mutations. Importantly, in rare patient s...Continue Reading

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Methods Mentioned

BETA
xenografts
biopsy
density gradient centrifugation
flow cytometry
biopsies
transfection
MDS
Fluorescence
chromosomal aberrations
chromosomal aberration

Software Mentioned

Aperio ImageScope
FACSDiva
MetaMorph
Prism
FlowJo

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