Osteoblasts protect AML cells from SDF-1-induced apoptosis

Kimberly N. Kremer, Amel Dudakovic, Meghan Elizabeth McGee Lawrence, Rachael L. Philips, Allan D. Hess, B. Douglas Smith, Andre J. Van Wijnen, Judith E. Karp, Scott H. Kaufmann, Jennifer J. Westendorf, Karen E. Hedin

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The bone marrow provides a protective environment for acute myeloid leukemia (AML) cells that often allows leukemic stem cells to survive standard chemotherapeutic regimens. Targeting these leukemic stem cells within the bone marrow is critical for preventing relapse. We recently demonstrated that SDF-1, a chemokine abundant in the bone marrow, induces apoptosis in AML cell lines and in patient samples expressing high levels of its receptor, CXCR4. Here we show that a subset of osteoblast lineage cells within the bone marrow can protect AML cells from undergoing apoptosis in response to the SDF-1 naturally present in that location. In co-culture systems, osteoblasts at various stages of differentiation protected AML cell lines and patient isolates from SDF-1-induced apoptosis. The differentiation of the osteoblast cell lines, MC3T3 and W-20-17, mediated this protection via a cell contact-independent mechanism. In contrast, bone marrow-derived mesenchymal cells, the precursors of osteoblasts, induced apoptosis in AML cells via a CXCR4-dependent mechanism and failed to protect AML cells from exogenously added SDF-1. These results indicate that osteoblasts in the process of differentiation potently inhibit the SDF-1-driven apoptotic pathway of CXCR4-expressing AML cells residing in the bone marrow. Drugs targeting this protective mechanism could potentially provide a new approach to treating AML by enhancing the SDF-1-induced apoptosis of AML cells residing within the bone marrow microenvironment.

Original languageEnglish (US)
Pages (from-to)1128-1137
Number of pages10
JournalJournal of Cellular Biochemistry
Volume115
Issue number6
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Osteoblasts
Myeloid Cells
Acute Myeloid Leukemia
Bone
Apoptosis
Bone Marrow
Cells
Stem cells
Cell Line
CXCR4 Receptors
Stem Cells
Chemokines
Cell culture
Drug Delivery Systems
Coculture Techniques
Bone Marrow Cells
Recurrence

Keywords

  • AML
  • APOPTOSIS
  • CXCL12
  • CXCR4
  • MESENCHYMAL
  • OSTEOBLAST
  • SDF-1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kremer, K. N., Dudakovic, A., McGee Lawrence, M. E., Philips, R. L., Hess, A. D., Smith, B. D., ... Hedin, K. E. (2014). Osteoblasts protect AML cells from SDF-1-induced apoptosis. Journal of Cellular Biochemistry, 115(6), 1128-1137. https://doi.org/10.1002/jcb.24755

Osteoblasts protect AML cells from SDF-1-induced apoptosis. / Kremer, Kimberly N.; Dudakovic, Amel; McGee Lawrence, Meghan Elizabeth; Philips, Rachael L.; Hess, Allan D.; Smith, B. Douglas; Van Wijnen, Andre J.; Karp, Judith E.; Kaufmann, Scott H.; Westendorf, Jennifer J.; Hedin, Karen E.

In: Journal of Cellular Biochemistry, Vol. 115, No. 6, 01.01.2014, p. 1128-1137.

Research output: Contribution to journalArticle

Kremer, KN, Dudakovic, A, McGee Lawrence, ME, Philips, RL, Hess, AD, Smith, BD, Van Wijnen, AJ, Karp, JE, Kaufmann, SH, Westendorf, JJ & Hedin, KE 2014, 'Osteoblasts protect AML cells from SDF-1-induced apoptosis', Journal of Cellular Biochemistry, vol. 115, no. 6, pp. 1128-1137. https://doi.org/10.1002/jcb.24755
Kremer, Kimberly N. ; Dudakovic, Amel ; McGee Lawrence, Meghan Elizabeth ; Philips, Rachael L. ; Hess, Allan D. ; Smith, B. Douglas ; Van Wijnen, Andre J. ; Karp, Judith E. ; Kaufmann, Scott H. ; Westendorf, Jennifer J. ; Hedin, Karen E. / Osteoblasts protect AML cells from SDF-1-induced apoptosis. In: Journal of Cellular Biochemistry. 2014 ; Vol. 115, No. 6. pp. 1128-1137.
@article{df64de844d2b4bd3b9daa1d2c640cd15,
title = "Osteoblasts protect AML cells from SDF-1-induced apoptosis",
abstract = "The bone marrow provides a protective environment for acute myeloid leukemia (AML) cells that often allows leukemic stem cells to survive standard chemotherapeutic regimens. Targeting these leukemic stem cells within the bone marrow is critical for preventing relapse. We recently demonstrated that SDF-1, a chemokine abundant in the bone marrow, induces apoptosis in AML cell lines and in patient samples expressing high levels of its receptor, CXCR4. Here we show that a subset of osteoblast lineage cells within the bone marrow can protect AML cells from undergoing apoptosis in response to the SDF-1 naturally present in that location. In co-culture systems, osteoblasts at various stages of differentiation protected AML cell lines and patient isolates from SDF-1-induced apoptosis. The differentiation of the osteoblast cell lines, MC3T3 and W-20-17, mediated this protection via a cell contact-independent mechanism. In contrast, bone marrow-derived mesenchymal cells, the precursors of osteoblasts, induced apoptosis in AML cells via a CXCR4-dependent mechanism and failed to protect AML cells from exogenously added SDF-1. These results indicate that osteoblasts in the process of differentiation potently inhibit the SDF-1-driven apoptotic pathway of CXCR4-expressing AML cells residing in the bone marrow. Drugs targeting this protective mechanism could potentially provide a new approach to treating AML by enhancing the SDF-1-induced apoptosis of AML cells residing within the bone marrow microenvironment.",
keywords = "AML, APOPTOSIS, CXCL12, CXCR4, MESENCHYMAL, OSTEOBLAST, SDF-1",
author = "Kremer, {Kimberly N.} and Amel Dudakovic and {McGee Lawrence}, {Meghan Elizabeth} and Philips, {Rachael L.} and Hess, {Allan D.} and Smith, {B. Douglas} and {Van Wijnen}, {Andre J.} and Karp, {Judith E.} and Kaufmann, {Scott H.} and Westendorf, {Jennifer J.} and Hedin, {Karen E.}",
year = "2014",
month = "1",
day = "1",
doi = "10.1002/jcb.24755",
language = "English (US)",
volume = "115",
pages = "1128--1137",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Osteoblasts protect AML cells from SDF-1-induced apoptosis

AU - Kremer, Kimberly N.

AU - Dudakovic, Amel

AU - McGee Lawrence, Meghan Elizabeth

AU - Philips, Rachael L.

AU - Hess, Allan D.

AU - Smith, B. Douglas

AU - Van Wijnen, Andre J.

AU - Karp, Judith E.

AU - Kaufmann, Scott H.

AU - Westendorf, Jennifer J.

AU - Hedin, Karen E.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - The bone marrow provides a protective environment for acute myeloid leukemia (AML) cells that often allows leukemic stem cells to survive standard chemotherapeutic regimens. Targeting these leukemic stem cells within the bone marrow is critical for preventing relapse. We recently demonstrated that SDF-1, a chemokine abundant in the bone marrow, induces apoptosis in AML cell lines and in patient samples expressing high levels of its receptor, CXCR4. Here we show that a subset of osteoblast lineage cells within the bone marrow can protect AML cells from undergoing apoptosis in response to the SDF-1 naturally present in that location. In co-culture systems, osteoblasts at various stages of differentiation protected AML cell lines and patient isolates from SDF-1-induced apoptosis. The differentiation of the osteoblast cell lines, MC3T3 and W-20-17, mediated this protection via a cell contact-independent mechanism. In contrast, bone marrow-derived mesenchymal cells, the precursors of osteoblasts, induced apoptosis in AML cells via a CXCR4-dependent mechanism and failed to protect AML cells from exogenously added SDF-1. These results indicate that osteoblasts in the process of differentiation potently inhibit the SDF-1-driven apoptotic pathway of CXCR4-expressing AML cells residing in the bone marrow. Drugs targeting this protective mechanism could potentially provide a new approach to treating AML by enhancing the SDF-1-induced apoptosis of AML cells residing within the bone marrow microenvironment.

AB - The bone marrow provides a protective environment for acute myeloid leukemia (AML) cells that often allows leukemic stem cells to survive standard chemotherapeutic regimens. Targeting these leukemic stem cells within the bone marrow is critical for preventing relapse. We recently demonstrated that SDF-1, a chemokine abundant in the bone marrow, induces apoptosis in AML cell lines and in patient samples expressing high levels of its receptor, CXCR4. Here we show that a subset of osteoblast lineage cells within the bone marrow can protect AML cells from undergoing apoptosis in response to the SDF-1 naturally present in that location. In co-culture systems, osteoblasts at various stages of differentiation protected AML cell lines and patient isolates from SDF-1-induced apoptosis. The differentiation of the osteoblast cell lines, MC3T3 and W-20-17, mediated this protection via a cell contact-independent mechanism. In contrast, bone marrow-derived mesenchymal cells, the precursors of osteoblasts, induced apoptosis in AML cells via a CXCR4-dependent mechanism and failed to protect AML cells from exogenously added SDF-1. These results indicate that osteoblasts in the process of differentiation potently inhibit the SDF-1-driven apoptotic pathway of CXCR4-expressing AML cells residing in the bone marrow. Drugs targeting this protective mechanism could potentially provide a new approach to treating AML by enhancing the SDF-1-induced apoptosis of AML cells residing within the bone marrow microenvironment.

KW - AML

KW - APOPTOSIS

KW - CXCL12

KW - CXCR4

KW - MESENCHYMAL

KW - OSTEOBLAST

KW - SDF-1

UR - http://www.scopus.com/inward/record.url?scp=84907422946&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907422946&partnerID=8YFLogxK

U2 - 10.1002/jcb.24755

DO - 10.1002/jcb.24755

M3 - Article

C2 - 24851270

AN - SCOPUS:84907422946

VL - 115

SP - 1128

EP - 1137

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 6

ER -