Title

In childhood acute lymphoblastic leukemia, blasts at different stages of immunophenotypic maturation have stem cell properties.

Document Type

Article

Publication Date

2008

Keywords

Animals, Antigens-CD19, Antigens-CD20, Antigens-CD34, B-Lymphocytes, Bone-Marrow-Transplantation, Cell-Differentiation, Cell-Line-Tumor, Cell-Lineage, Cell-Proliferation, Cell-Separation, Child-Preschool, Flow-Cytometry, Gene-Expression-Regulation-Leukemic, Humans, Immunoglobulins, Immunophenotyping, Infant, Infant-Newborn, Mice-Inbred-NOD, Mice-SCID, Neoplastic-Stem-Cells, Phenotype, Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma, Transplantation-Heterologous

JAX Source

Cancer Cell 2008 Jul; 14(1):47-58.

Abstract

We examined the leukemic stem cell potential of blasts at different stages of maturation in childhood acute lymphoblastic leukemia (ALL). Human leukemic bone marrow was transplanted intrafemorally into NOD/scid mice. Cells sorted using the B precursor differentiation markers CD19, CD20, and CD34 were isolated from patient samples and engrafted mice before serial transplantation into primary or subsequent (up to quaternary) recipients. Surprisingly, blasts representative of all of the different maturational stages were able to reconstitute and reestablish the complete leukemic phenotype in vivo. Sorted blast populations mirrored normal B precursor cells with transcription of a number of stage-appropriate genes. These observations inform a model for leukemia-propagating stem cells in childhood ALL.