IGFBP7 Induces Differentiation and Loss of Survival of Human Acute Myeloid Leukemia Stem Cells without Affecting Normal Hematopoiesis

Han J. M. P. Verhagen, Noortje van Gils, Tania Martiañez, Anna van Rhenen, Arjo Rutten, Fedor Denkers, David C. de Leeuw, Marjon A. Smit, Mei-Ling Tsui, Louise L. E. de Vos Klootwijk, Renee X. Menezes, Meyram Çil, Margaretha G. M. Roemer, Eline Vermue, Stan Heukelom, Sonja Zweegman, Jeroen J. W. M. Janssen, Gert J. Ossenkoppele, Gerrit Jan Schuurhuis, Linda Smit

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)


Leukemic stem cells (LSCs) are thought to be the major cause of the recurrence of acute myeloid leukemia (AML) due to their potential for self-renewal. To identify therapeutic strategies targeting LSCs, while sparing healthy hematopoietic stem cells (HSCs), we performed gene expression profiling of LSCs, HSCs, and leukemic progenitors all residing within the same AML bone marrow and identified insulin-like growth factor-binding protein 7 (IGFBP7) as differentially expressed. Low IGFBP7 is a feature of LSCs and is associated with reduced chemotherapy sensitivity. Enhancing IGFBP7 by overexpression or addition of recombinant human IGFBP7 (rhIGFBP7) resulted in differentiation, inhibition of cell survival, and increased chemotherapy sensitivity of primary AML cells. Adding rhIGFBP7 reduced leukemic stem and/or progenitor survival and reversed a stem-like gene signature, but it had no influence on normal hematopoietic stem cell survival. Our data suggest a potential clinical utility of the addition of rhIGFBP7 to current chemotherapy regimens to decrease AML relapse rates.

Original languageEnglish
Pages (from-to)3021-3035.e5
JournalCell reports
Issue number11
Early online date2018
Publication statusPublished - 11 Dec 2018

Cite this