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[Cancer Research 52, 4458-4466, August 15, 1992]
© 1992 American Association for Cancer Research

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In Vitro Growth Modulation by L-Ascorbic Acid of Colony-forming Cells from Bone Marrow of Patients with Myelodysplastic Syndromes1

Chan H. Park2, Bruce F. Kimler, David Bodensteiner, Sean R. Lynch and Ruth S. Hassanein

Departments of Medicine [C. H. P., D. B., S. R. L.], Radiation Oncology [B. F. K.], and Biometry [R. S. H.], University of Kansas Medical Center, Kansas City, Kansas 66160

In vitro colony growth was studied on bone marrow cells from 51 patients with myelodysplastic syndromes (MDS), using a cell culture method with the unique feature of daily feeding, in an effort to gain insight into the pathophysiology of MDS and to assess the clinical utility of this cell culture assay. The colony growth pattern of MDS marrow cells is remarkably similar to that of acute myeloid leukemia but quite dissimilar from that of normal marrow, in support of a common pathophysiological mechanism for these two disorders. In particular, L-ascorbic acid (LAA) enhanced colony growth in 30% and suppressed growth in 16% of cases, a finding also similar to that in acute myeloid leukemia, indicating a unique growth requirement which may be explored for therapeutic purposes. Further, these LAA effects have prognostic value, with LAA-sensitive (both LAA-enhanced and LAA-suppressed) cases displaying shorter survivals than LAA-insensitive cases (median survival of 5 months versus 18 months; P = 0.011). This prognostic value is independent of, and more powerful than, bone marrow blasts; the median survival was 18 months for <5% bone marrow blasts and 8 months for >5% bone marrow blasts (P = 0.044). These two risk factors can be used together to identify patients with an extremely good or an extremely poor prognosis. This study establishes the clinical usefulness of the LAA effect in MDS as a prognostic factor and provides a new lead to explore in understanding differential biochemical/molecular events and, possibly, a new therapeutic approach to the management of MDS.

1 Supported by a grant (RO1 CA 20717), a Research Career Development Award to C. H. P. (K04 CA 00534) from the NIH, and the A. S. and Minnie Q. Underwood Fund.

2 To whom requests for reprints should be addressed, at Division of Oncology/Hematology, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430.

Received 2/21/92. Accepted 6/ 4/92.







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1992 by the American Association for Cancer Research.