In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells

Bradley T. Messmer, Davorka Messmer, Steven L. Allen, Jonathan E. Kolitz, Prasad Kudalkar, Denise Cesar, Elizabeth J. Murphy, Prasad Koduru, Manlio Ferrarini, Simona Zupo, Giovanna Cutrona, Rajendra N. Damle, Tarun Wasil, Kanti R. Rai, Marc K. Hellerstein, Nicholas Chiorazzi

Research output: Contribution to journalArticle

437 Citations (Scopus)

Abstract

Due to its relatively slow clinical progression, B cell chronic lymphocytic leukemia (B-CLL) is classically described as a disease of accumulation rather than proliferation. However, evidence for various forms of clonal evolution suggests that B-CLL clones may be more dynamic than previously assumed. We used a nonradioactive, stable isotopic labeling method to measure B-CLL cell kinetics in vivo. Nineteen patients drank an aliquot of deuterated water ( 2H2O) daily for 84 days, and 2H incorporation into the deoxyribose moiety of DNA of newly divided B-CLL cells was measured by gas chromatography/mass spectrometry, during and after the labeling period. Birth rates were calculated from the kinetic profiles. Death rates were defined as the difference between calculated birth and growth rates. These analyses demonstrated that the leukemic cells of each patient had definable and often substantial birth rates, varying from 0.1% to greater than 1.0% of the entire clone per day. Those patients with birth rates greater than 0.35% per day were much more likely to exhibit active or to develop progressive disease than those with lower birth rates Thus, B-CLL is not a static disease that results simply from accumulation of long-lived lymphocytes. Rather, it is a dynamic process composed also of cells that proliferate and die, often at appreciable levels. The extent to which this turnover occurs has not been previously appreciated. A correlation between birth rates and disease activity and progression appears to exist, which may help identify patients at risk for worsening disease in advance of clinical deterioration.

Original languageEnglish (US)
Pages (from-to)755-764
Number of pages10
JournalJournal of Clinical Investigation
Volume115
Issue number3
DOIs
StatePublished - Mar 2005

Fingerprint

Birth Rate
B-Cell Chronic Lymphocytic Leukemia
Clone Cells
Clonal Evolution
Deoxyribose
Gas Chromatography-Mass Spectrometry
Disease Progression
Lymphocytes
Mortality
Water
DNA
Growth

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Messmer, B. T., Messmer, D., Allen, S. L., Kolitz, J. E., Kudalkar, P., Cesar, D., ... Chiorazzi, N. (2005). In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. Journal of Clinical Investigation, 115(3), 755-764. https://doi.org/10.1172/JCI200523409

In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. / Messmer, Bradley T.; Messmer, Davorka; Allen, Steven L.; Kolitz, Jonathan E.; Kudalkar, Prasad; Cesar, Denise; Murphy, Elizabeth J.; Koduru, Prasad; Ferrarini, Manlio; Zupo, Simona; Cutrona, Giovanna; Damle, Rajendra N.; Wasil, Tarun; Rai, Kanti R.; Hellerstein, Marc K.; Chiorazzi, Nicholas.

In: Journal of Clinical Investigation, Vol. 115, No. 3, 03.2005, p. 755-764.

Research output: Contribution to journalArticle

Messmer, BT, Messmer, D, Allen, SL, Kolitz, JE, Kudalkar, P, Cesar, D, Murphy, EJ, Koduru, P, Ferrarini, M, Zupo, S, Cutrona, G, Damle, RN, Wasil, T, Rai, KR, Hellerstein, MK & Chiorazzi, N 2005, 'In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells', Journal of Clinical Investigation, vol. 115, no. 3, pp. 755-764. https://doi.org/10.1172/JCI200523409
Messmer, Bradley T. ; Messmer, Davorka ; Allen, Steven L. ; Kolitz, Jonathan E. ; Kudalkar, Prasad ; Cesar, Denise ; Murphy, Elizabeth J. ; Koduru, Prasad ; Ferrarini, Manlio ; Zupo, Simona ; Cutrona, Giovanna ; Damle, Rajendra N. ; Wasil, Tarun ; Rai, Kanti R. ; Hellerstein, Marc K. ; Chiorazzi, Nicholas. / In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. In: Journal of Clinical Investigation. 2005 ; Vol. 115, No. 3. pp. 755-764.
@article{4bff70f5748e41e08ea12f78ef7acf56,
title = "In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells",
abstract = "Due to its relatively slow clinical progression, B cell chronic lymphocytic leukemia (B-CLL) is classically described as a disease of accumulation rather than proliferation. However, evidence for various forms of clonal evolution suggests that B-CLL clones may be more dynamic than previously assumed. We used a nonradioactive, stable isotopic labeling method to measure B-CLL cell kinetics in vivo. Nineteen patients drank an aliquot of deuterated water ( 2H2O) daily for 84 days, and 2H incorporation into the deoxyribose moiety of DNA of newly divided B-CLL cells was measured by gas chromatography/mass spectrometry, during and after the labeling period. Birth rates were calculated from the kinetic profiles. Death rates were defined as the difference between calculated birth and growth rates. These analyses demonstrated that the leukemic cells of each patient had definable and often substantial birth rates, varying from 0.1{\%} to greater than 1.0{\%} of the entire clone per day. Those patients with birth rates greater than 0.35{\%} per day were much more likely to exhibit active or to develop progressive disease than those with lower birth rates Thus, B-CLL is not a static disease that results simply from accumulation of long-lived lymphocytes. Rather, it is a dynamic process composed also of cells that proliferate and die, often at appreciable levels. The extent to which this turnover occurs has not been previously appreciated. A correlation between birth rates and disease activity and progression appears to exist, which may help identify patients at risk for worsening disease in advance of clinical deterioration.",
author = "Messmer, {Bradley T.} and Davorka Messmer and Allen, {Steven L.} and Kolitz, {Jonathan E.} and Prasad Kudalkar and Denise Cesar and Murphy, {Elizabeth J.} and Prasad Koduru and Manlio Ferrarini and Simona Zupo and Giovanna Cutrona and Damle, {Rajendra N.} and Tarun Wasil and Rai, {Kanti R.} and Hellerstein, {Marc K.} and Nicholas Chiorazzi",
year = "2005",
month = "3",
doi = "10.1172/JCI200523409",
language = "English (US)",
volume = "115",
pages = "755--764",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "3",

}

TY - JOUR

T1 - In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells

AU - Messmer, Bradley T.

AU - Messmer, Davorka

AU - Allen, Steven L.

AU - Kolitz, Jonathan E.

AU - Kudalkar, Prasad

AU - Cesar, Denise

AU - Murphy, Elizabeth J.

AU - Koduru, Prasad

AU - Ferrarini, Manlio

AU - Zupo, Simona

AU - Cutrona, Giovanna

AU - Damle, Rajendra N.

AU - Wasil, Tarun

AU - Rai, Kanti R.

AU - Hellerstein, Marc K.

AU - Chiorazzi, Nicholas

PY - 2005/3

Y1 - 2005/3

N2 - Due to its relatively slow clinical progression, B cell chronic lymphocytic leukemia (B-CLL) is classically described as a disease of accumulation rather than proliferation. However, evidence for various forms of clonal evolution suggests that B-CLL clones may be more dynamic than previously assumed. We used a nonradioactive, stable isotopic labeling method to measure B-CLL cell kinetics in vivo. Nineteen patients drank an aliquot of deuterated water ( 2H2O) daily for 84 days, and 2H incorporation into the deoxyribose moiety of DNA of newly divided B-CLL cells was measured by gas chromatography/mass spectrometry, during and after the labeling period. Birth rates were calculated from the kinetic profiles. Death rates were defined as the difference between calculated birth and growth rates. These analyses demonstrated that the leukemic cells of each patient had definable and often substantial birth rates, varying from 0.1% to greater than 1.0% of the entire clone per day. Those patients with birth rates greater than 0.35% per day were much more likely to exhibit active or to develop progressive disease than those with lower birth rates Thus, B-CLL is not a static disease that results simply from accumulation of long-lived lymphocytes. Rather, it is a dynamic process composed also of cells that proliferate and die, often at appreciable levels. The extent to which this turnover occurs has not been previously appreciated. A correlation between birth rates and disease activity and progression appears to exist, which may help identify patients at risk for worsening disease in advance of clinical deterioration.

AB - Due to its relatively slow clinical progression, B cell chronic lymphocytic leukemia (B-CLL) is classically described as a disease of accumulation rather than proliferation. However, evidence for various forms of clonal evolution suggests that B-CLL clones may be more dynamic than previously assumed. We used a nonradioactive, stable isotopic labeling method to measure B-CLL cell kinetics in vivo. Nineteen patients drank an aliquot of deuterated water ( 2H2O) daily for 84 days, and 2H incorporation into the deoxyribose moiety of DNA of newly divided B-CLL cells was measured by gas chromatography/mass spectrometry, during and after the labeling period. Birth rates were calculated from the kinetic profiles. Death rates were defined as the difference between calculated birth and growth rates. These analyses demonstrated that the leukemic cells of each patient had definable and often substantial birth rates, varying from 0.1% to greater than 1.0% of the entire clone per day. Those patients with birth rates greater than 0.35% per day were much more likely to exhibit active or to develop progressive disease than those with lower birth rates Thus, B-CLL is not a static disease that results simply from accumulation of long-lived lymphocytes. Rather, it is a dynamic process composed also of cells that proliferate and die, often at appreciable levels. The extent to which this turnover occurs has not been previously appreciated. A correlation between birth rates and disease activity and progression appears to exist, which may help identify patients at risk for worsening disease in advance of clinical deterioration.

UR - http://www.scopus.com/inward/record.url?scp=20044372326&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20044372326&partnerID=8YFLogxK

U2 - 10.1172/JCI200523409

DO - 10.1172/JCI200523409

M3 - Article

VL - 115

SP - 755

EP - 764

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 3

ER -