Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI105553

Studies of Cellular Proliferation in Human Leukemia. I. Estimation of Growth Rates of Leukemic and Normal Hematopoietic Cells in Two Adults with Acute Leukemia Given Single Injections of Tritiated Thymidine

Bayard Clarkson, Takeshi Ohkita, Kazuo Ota, and Jerrold Fried

Division of Clinical Chemotherapy, Sloan-Kettering Institute for Cancer Research, New York, N. Y.

Division of Biophysics, Sloan-Kettering Institute for Cancer Research, New York, N. Y.

Department of Medicine, Memorial and James Ewing Hospitals for Cancer and Allied Diseases and Cornell University Medical College, New York, N. Y.

†

Address requests for reprints to Dr. Bayard Clarkson, Sloan-Kettering Institute for Cancer Research, New York, N. Y.

‡

Supported by U. S. Public Health Service graduate training grant 5T4 CA5015 from the National Cancer Institute.

*

Submitted for publication February 8, 1966; accepted December 9, 1966.

This investigation was supported in part by research grants CA-03215, CA-05826, and CA-08748 from the National Cancer Institute, U. S. Public Health Service.

Presented in part at the Fifty-seventh Annual Meeting of the American Society for Clinical Investigation, Atlantic City, N. J., May 1965.

Find articles by Clarkson, B. in: PubMed | Google Scholar

Division of Clinical Chemotherapy, Sloan-Kettering Institute for Cancer Research, New York, N. Y.

Division of Biophysics, Sloan-Kettering Institute for Cancer Research, New York, N. Y.

Department of Medicine, Memorial and James Ewing Hospitals for Cancer and Allied Diseases and Cornell University Medical College, New York, N. Y.

†

Address requests for reprints to Dr. Bayard Clarkson, Sloan-Kettering Institute for Cancer Research, New York, N. Y.

‡

Supported by U. S. Public Health Service graduate training grant 5T4 CA5015 from the National Cancer Institute.

*

Submitted for publication February 8, 1966; accepted December 9, 1966.

This investigation was supported in part by research grants CA-03215, CA-05826, and CA-08748 from the National Cancer Institute, U. S. Public Health Service.

Presented in part at the Fifty-seventh Annual Meeting of the American Society for Clinical Investigation, Atlantic City, N. J., May 1965.

Find articles by Ohkita, T. in: PubMed | Google Scholar

Division of Clinical Chemotherapy, Sloan-Kettering Institute for Cancer Research, New York, N. Y.

Division of Biophysics, Sloan-Kettering Institute for Cancer Research, New York, N. Y.

Department of Medicine, Memorial and James Ewing Hospitals for Cancer and Allied Diseases and Cornell University Medical College, New York, N. Y.

†

Address requests for reprints to Dr. Bayard Clarkson, Sloan-Kettering Institute for Cancer Research, New York, N. Y.

‡

Supported by U. S. Public Health Service graduate training grant 5T4 CA5015 from the National Cancer Institute.

*

Submitted for publication February 8, 1966; accepted December 9, 1966.

This investigation was supported in part by research grants CA-03215, CA-05826, and CA-08748 from the National Cancer Institute, U. S. Public Health Service.

Presented in part at the Fifty-seventh Annual Meeting of the American Society for Clinical Investigation, Atlantic City, N. J., May 1965.

Find articles by Ota, K. in: PubMed | Google Scholar

Division of Clinical Chemotherapy, Sloan-Kettering Institute for Cancer Research, New York, N. Y.

Division of Biophysics, Sloan-Kettering Institute for Cancer Research, New York, N. Y.

Department of Medicine, Memorial and James Ewing Hospitals for Cancer and Allied Diseases and Cornell University Medical College, New York, N. Y.

†

Address requests for reprints to Dr. Bayard Clarkson, Sloan-Kettering Institute for Cancer Research, New York, N. Y.

‡

Supported by U. S. Public Health Service graduate training grant 5T4 CA5015 from the National Cancer Institute.

*

Submitted for publication February 8, 1966; accepted December 9, 1966.

This investigation was supported in part by research grants CA-03215, CA-05826, and CA-08748 from the National Cancer Institute, U. S. Public Health Service.

Presented in part at the Fifty-seventh Annual Meeting of the American Society for Clinical Investigation, Atlantic City, N. J., May 1965.

Find articles by Fried, J. in: PubMed | Google Scholar

Published April 1, 1967 - More info

Published in Volume 46, Issue 4 on April 1, 1967
J Clin Invest. 1967;46(4):506–529. https://doi.org/10.1172/JCI105553.
© 1967 The American Society for Clinical Investigation
Published April 1, 1967 - Version history
View PDF
Abstract

Two adults with rapidly progressive acute myeloblastic and myelomonoblastic leukemia were given single injections of tritiated thymidine, and measurements were made of the growth rates of their leukemic and normal hematopoietic cells by radioautographic methods. Although almost all leukemic blasts in both marrow and blood were metabolically active as shown by their ability to incorporate tritiated uridine and leucine in vitro, only 5.6% and 6.1% of the blasts in the marrow and even fewer in the blood incorporated tritiated thymidine. The mitotic indexes of the marrow blasts were 0.66% and 0.52%; no circulating blasts were dividing. The mean generation times of the actively proliferating blasts were estimated to be 49 and 83 hours. This cannot be equated with the doubling time of the total leukemic population as there is evidence that many blasts fail to continue dividing and die. The mean durations of the phases of the blasts' mitotic cycles were as follows: DNA synthesis (S) = 22 and 19 hours, premitosis (G2) = 3 hours, mitosis (M) = 0.47 and 0.62 hour (minimal estimates), and postmitosis (G1) = 24 and 61 hours. In both patients the maximal mean transit time of the blasts in the blood was 36 hours, and the minimal numbers of actively dividing blasts present were 1.6 and 2.6 × 109 per kg of body weight.

Estimates were also made of the rates of proliferation and maturation of the residual normal erythrocytic and granulocytic cells in these two patients. Although total production was markedly diminished because of reduction in the number of normal elements, the relatively few remaining normal cells appeared to be dividing and maturing at rates that are about the same or only slightly slower than those found in normal subjects.

We conclude that main reason leukemic blasts displace normal hematopoietic precursors in acute leukemia is that the blasts largely fail to differentiate. Many die but many others persist in the marrow and elsewhere as primitive cells and continue to proliferate. As the blasts accumulate, they gradually displace the normal hematopoietic cells, most of which continue their normal course of differentiation and leave the marrow as nondividing mature cells. It is not known why the over-all production of normal cells is not adequately increased to compensate for the anemia, granulocytopenia, and thrombocytopenia that develop, but apparently the leukemic cells somehow interfere with the proliferation or differentiation or both of normal stem cells.

Browse pages

Click on an image below to see the page. View PDF of the complete article

icon of scanned page 506
page 506
icon of scanned page 507
page 507
icon of scanned page 508
page 508
icon of scanned page 509
page 509
icon of scanned page 510
page 510
icon of scanned page 511
page 511
icon of scanned page 512
page 512
icon of scanned page 513
page 513
icon of scanned page 514
page 514
icon of scanned page 515
page 515
icon of scanned page 516
page 516
icon of scanned page 517
page 517
icon of scanned page 518
page 518
icon of scanned page 519
page 519
icon of scanned page 520
page 520
icon of scanned page 521
page 521
icon of scanned page 522
page 522
icon of scanned page 523
page 523
icon of scanned page 524
page 524
icon of scanned page 525
page 525
icon of scanned page 526
page 526
icon of scanned page 527
page 527
icon of scanned page 528
page 528
icon of scanned page 529
page 529
Version history
  • Version 1 (April 1, 1967): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts