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Constitutive function of the Ikaros transcription factor in primary leukemia cells from pediatric newly diagnosed
Fatih M Uckun1, Hong Ma, Rita Ishkhanian
1Systems Immunobiology Laboratory and Developmental Therapeutics Program, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California, United States of America ; Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America ; Developmental Therapeutics Program, USC Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
Abstract:
We examined the constitutive function of the Ikaros (IK) transcription factor in blast cells from pediatric B-precursor acute lymphoblastic leukemia (BPL) patients using multiple assay platforms and bioinformatics tools. We found no evidence of diminished IK expression or function for primary cells from high-risk BPL patients including a Philadelphia chromosome (Ph)(+) subset. Relapse clones as well as very aggressive in vivo clonogenic leukemic B-cell precursors isolated from spleens of xenografted NOD/SCID mice that developed overt leukemia after inoculation with primary leukemic cells of patients with BPL invariably and abundantly expressed intact IK protein. These results demonstrate that a lost or diminished IK function is not a characteristic feature of leukemic cells in Ph(+) or Ph(-) high-risk BPL.
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