Abstract 1507: Heterogeneity of CD34 and CD38 expression in adult acute B lymphoblastic leukemia cells is reversible and not hierarchically organized

Abstract

Abstract The existence and identification of leukemia stem cells in adult acute B lymphoblastic leukemia (B-ALL) remain controversial. We examined whether adult B-ALL is hierarchically organized into phenotypically distinct subpopulations of leukemogenic and non-leukemogenic cells or whether most B-ALL cells retain leukemogenic capacity, irrespective of their immunophenotypes. Cells from CD34+CD38-, CD34+CD38+, and CD34-CD38+ subpopulations of primary adult B-ALL xenografts were shown to be capable of reconstituting the original leukemia in NOD-scid-IL2Rg-/- mice. We found that primary leukemia cells from 11 of 25 adult B-ALL patients with different expression profiles of CD34 and CD38 proliferated robustly and became CD34-CD38+ after being co-cultured with OP9 stromal cells. Surprisingly, cultured CD34-CD38+ B-ALL cells were able to reestablish the complete leukemic phenotype in xenografts. Transcriptomic analysis of CD34+CD38-, CD34+CD38+, and CD34-CD38+ fractions purified directly from xenografts and CD34-CD38+ cells from culture revealed no significantly distinct expression profiles of transcription factors among these populations. Furthermore, 5.7% of single adult primary B-ALL cells engrafted in vivo. These observations suggest that adult B-ALL follows the stochastic stem cell model and that the heterogeneity of CD34 and CD38 expression in B-ALL is reversibly dependent on the microenvironment and is not hierarchically organized. Citation Format: Zhiwu Jiang, Manman Deng, Yi Lu, Bing Xu, Peng Li. Heterogeneity of CD34 and CD38 expression in adult acute B lymphoblastic leukemia cells is reversible and not hierarchically organized. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1507. doi:10.1158/1538-7445.AM2015-1507