Hematopoietic stem cells can be separated from leukemic cells in a subgroup of adult acute lymphoblastic leukemia patients

Abstract

In B-cell acute lymphoblastic leukemia (B-ALL) separation of normal hematopoietic stem cells (HSC) has so far been limited to a subgroup of patients. As aldehyde dehydrogenase (ALDH)-activity is enriched in various stem cells we investigated its value for HSC isolation in adult B-ALL. Based on ALDH-activity patients could be stratified in ALDH-numerous (≥1.9% ALDH⁺cells) and ALDH-rare (<1.9% ALDH⁺cells) cases. In ALDH-rare B-ALL clonal-marker negative HSC could be separated by the CD34⁺CD38⁻ALDH⁺ phenotype, whereas this separation was not possible in ALDH-numerous B-ALL. Functional analysis confirmed the HSC-potential of isolated cells, which were uniformly CD19-negative. However, addition of ALDH-activity further improved HSC-purity. In summary, we provide a method to separate functionally normal HSC from leukemic cells in a subgroup of B-ALL patients that can be identified prospectively. This protocol thereby facilitates comparative analyses of matched HSC and leukemic cells in order to improve our understanding of leukemia evolution.

Keywords:

• B-cell acute lymphoblastic leukemia
• hematopoietic stem cells
• aldehyde dehydrogenase

Acknowledgments

This work was supported by research funding from the German Research Foundation DFG (SFB 873; subprojects A13 to C. L., B07 to A. D. H., and Z02 to V. E.) and the Kind-Stiftung [061015] (to A. D. H and C. L.).

The authors thank Michaela Brough for the performance of FISH, Bettina Maier, Borhan R. Saeed and Laura Poisa-Beiro for their technical help, Katrin Miesala for the isolation of primary cells and Anke Diehlmann for the isolation and culture of human MSCs. We are grateful to all clinicians in the Hematology Department of Heidelberg University Hospital for their contribution in the collection of patient materials and patients and healthy donors who participated in this study.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online. at http://dx.doi.org/10.1080/10428194.2016.1236378.