Early suppressive effects of chemotherapy on recovery of bone marrow megakaryocyte precursors

Possible relationship to platelet recovery

M. Kim Warren, Joanne Zujewski, Wendy L. Rose, Janet M. Szabo, Joyce A. O'Shaughnessy, David C. Halverson, Kenneth H Cowan, Ronald E. Gress, Gretchen N. Schwartz

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

This study utilized a recently developed culture and quantitation system to detect megakaryocyte precursors in CD34+ bone marrow cells from normal donors and breast cancer patients treated with 5-fluorouracil, leucovorin, adriamycin and cyclophosphamide (FLAC). Bone marrow was obtained from patients before and then after their first cycle of FLAC once blood cell counts had recovered. CD34+ cells were isolated and placed in liquid culture with growth factors to stimulate proliferation and lineage commitment. Absorbance values from an enzyme-linked immunosorbent assay were used to quantitate expression of platelet glycoprotein GPIIb/IIIa. There was an increase in absorbance with increasing numbers of cells seeded per culture that was associated with an increase in the number of megakaryocyte lineage cells produced. After 10 days in liquid culture, absorbance values for expression of GPIIb/IIIa from 2,000 normal donor and pre-chemotherapy CD34+ marrow cells were ≥ 1.0. Absorbance values from cultures of post-chemotherapy CD34+ cells from four patients were similar to values from pre-chemotherapy CD34+ cells. In contrast, absorbance values from cultures of post-chemotherapy CD34+ cells from two other patients were low (absorbance <0.5). Low absorbance values for GPIIb/IIIa expression indicate that megakaryocyte production from those CD34+ cells was reduced. Both of those patients developed prolonged thrombocytopenia and platelet nadirs of less than 20,000/μl during FLAC chemotherapy. In contrast, only one out of four patients whose cultures of post-chemotherapy CD34+ cells had absorbance values ≥ 1.0 developed platelet nadirs less than 20,000/μl. These results suggest that low platelet nadirs and delayed platelet recovery may be associated with suppressive effects of chemotherapy on recovery of megakaryocyte precursors.

Original languageEnglish (US)
Pages (from-to)31-37
Number of pages7
JournalSTEM CELLS
Volume14
Issue numberSUPPL. 1
StatePublished - Dec 1 1996

Fingerprint

Megakaryocytes
Blood Platelets
Bone Marrow
Drug Therapy
Leucovorin
Fluorouracil
Doxorubicin
Cyclophosphamide
Tissue Donors
Integrin beta3
Blood Cell Count
Bone Marrow Cells
Thrombocytopenia
Intercellular Signaling Peptides and Proteins
Cell Count
Enzyme-Linked Immunosorbent Assay
Breast Neoplasms

Keywords

  • CD34 cells
  • Chemotherapy
  • ELISA
  • Glycoprotein GPIIb/IIIa
  • Megakaryocytes

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Warren, M. K., Zujewski, J., Rose, W. L., Szabo, J. M., O'Shaughnessy, J. A., Halverson, D. C., ... Schwartz, G. N. (1996). Early suppressive effects of chemotherapy on recovery of bone marrow megakaryocyte precursors: Possible relationship to platelet recovery. STEM CELLS, 14(SUPPL. 1), 31-37.

Early suppressive effects of chemotherapy on recovery of bone marrow megakaryocyte precursors : Possible relationship to platelet recovery. / Warren, M. Kim; Zujewski, Joanne; Rose, Wendy L.; Szabo, Janet M.; O'Shaughnessy, Joyce A.; Halverson, David C.; Cowan, Kenneth H; Gress, Ronald E.; Schwartz, Gretchen N.

In: STEM CELLS, Vol. 14, No. SUPPL. 1, 01.12.1996, p. 31-37.

Research output: Contribution to journalArticle

Warren, MK, Zujewski, J, Rose, WL, Szabo, JM, O'Shaughnessy, JA, Halverson, DC, Cowan, KH, Gress, RE & Schwartz, GN 1996, 'Early suppressive effects of chemotherapy on recovery of bone marrow megakaryocyte precursors: Possible relationship to platelet recovery', STEM CELLS, vol. 14, no. SUPPL. 1, pp. 31-37.
Warren MK, Zujewski J, Rose WL, Szabo JM, O'Shaughnessy JA, Halverson DC et al. Early suppressive effects of chemotherapy on recovery of bone marrow megakaryocyte precursors: Possible relationship to platelet recovery. STEM CELLS. 1996 Dec 1;14(SUPPL. 1):31-37.
Warren, M. Kim ; Zujewski, Joanne ; Rose, Wendy L. ; Szabo, Janet M. ; O'Shaughnessy, Joyce A. ; Halverson, David C. ; Cowan, Kenneth H ; Gress, Ronald E. ; Schwartz, Gretchen N. / Early suppressive effects of chemotherapy on recovery of bone marrow megakaryocyte precursors : Possible relationship to platelet recovery. In: STEM CELLS. 1996 ; Vol. 14, No. SUPPL. 1. pp. 31-37.
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abstract = "This study utilized a recently developed culture and quantitation system to detect megakaryocyte precursors in CD34+ bone marrow cells from normal donors and breast cancer patients treated with 5-fluorouracil, leucovorin, adriamycin and cyclophosphamide (FLAC). Bone marrow was obtained from patients before and then after their first cycle of FLAC once blood cell counts had recovered. CD34+ cells were isolated and placed in liquid culture with growth factors to stimulate proliferation and lineage commitment. Absorbance values from an enzyme-linked immunosorbent assay were used to quantitate expression of platelet glycoprotein GPIIb/IIIa. There was an increase in absorbance with increasing numbers of cells seeded per culture that was associated with an increase in the number of megakaryocyte lineage cells produced. After 10 days in liquid culture, absorbance values for expression of GPIIb/IIIa from 2,000 normal donor and pre-chemotherapy CD34+ marrow cells were ≥ 1.0. Absorbance values from cultures of post-chemotherapy CD34+ cells from four patients were similar to values from pre-chemotherapy CD34+ cells. In contrast, absorbance values from cultures of post-chemotherapy CD34+ cells from two other patients were low (absorbance <0.5). Low absorbance values for GPIIb/IIIa expression indicate that megakaryocyte production from those CD34+ cells was reduced. Both of those patients developed prolonged thrombocytopenia and platelet nadirs of less than 20,000/μl during FLAC chemotherapy. In contrast, only one out of four patients whose cultures of post-chemotherapy CD34+ cells had absorbance values ≥ 1.0 developed platelet nadirs less than 20,000/μl. These results suggest that low platelet nadirs and delayed platelet recovery may be associated with suppressive effects of chemotherapy on recovery of megakaryocyte precursors.",
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