Abstract
Several hematological diseases are characterised by oscillations of various blood cell populations. Two of these are a variant of chronic myelogenous leukemia (CML) and cyclical neutropenia (CN). These oscillations typically have long periods ranging from 20 to 60 days, despite the fact that the stem cell cycling time is thought to be of the order of 2–3 days. Clinical data from humans and laboratory data from the grey collie animal model of CN is suggestive of the idea that these long period oscillations may also contain higher frequency spiky oscillations. We show how such oscillations can be understood in the context of slow periodic stem cell oscillations, by analysing a two component differential-delay equation model of stem cell and neutrophil populations.
References
Bernard, S., Belair, J., Mackey, M.: Oscillations in cyclical neutropenia: New evidence based on mathematical modeling. J. Theor. Biol. 223 (2003)
Borge O., Ramsfjell V., Cui L., Jacobsen S. (1997). Ability of early acting cytokines to directly promote survival and suppress apoptosis of human primitive CD34+CD38- bone marrow cells with multilineage potential at the single cell level: Key role of thrombopoietin. Blood 90:2282–2292
Chikkappa G., Borner A.H.B.G., Chanana A.D., Cronkite E.P., Ohl S., Pavelec M., Robertso J.S. (1976). Periodic oscillation of blood leukocytes, platelets, and reticulocytes in a patient with chronic myelocytic leukemia. Blood 47:1023–1030
Colijn, C., Mackey, M.: A mathematical model of hematopoiesis: I. Periodic chronic myelogenous leukemia. J. Theor. Biol. (2005a in press)
Colijn, C., Mackey, M.: A mathematical model of hematopoiesis: II. Cyclical neutropenia. J. Theor. Biol. (2005b in press)
Dale D., Bonilla M., Davis M., Nakanishi A., Hammond W., Kurtzberg J., Wang W., Jakubowski A., Winton E., Lalezari P., Robinson W., Glaspy J., Emerson S., Gabrilove J., Vincent M., Boxer L. (1993). A randomized controlled phase iii trial of recombinant human granulocyte colony stimulating factor (filgrastim) for treatment of severe chronic neutropenia. Blood 81:2496–2502
Delobel J., Charbord P., Passa P., Bernard J. (1973). Evolution cyclique spontanée de la leucocytose dans un cas de leucémie myéloide chronique. Nouv. Rev. franc Hémat. 13:221–228
Fortin P., Mackey M. (1999). Periodic chronic myelogenous leukemia: Spectral analysis of blood cell counts and etiological implications. Br. J. Haematol. 104:336–245
Fowler A., Mackey M. (2002). Relaxation oscillations in a class of delay differential equations. SIAM J. Appl. Math. 63:299–323
Gatti, R. A., Robinson, W. A., Deinare, A. S., Nesbit, M., J. J. McCullough, M. B. . R. A. G.: Cyclic leukocytosis in chronic myelogenous leukemia. Blood 41, 771–782 (1973)
Haurie C., Mackey M.C., Dale D.C. (1998). Cyclical neutropenia and other periodic hematological diseases: a review of mechanisms and mathematical models. Blood 92:2629–2640
Haurie, C., Mackey, M.C., Dale, D.C.: Occurrence of periodic oscillations in the differential blood counts of congenital, idiopathic and cyclical neutropenic patients before and during treatment with G-CSF. Exper. Hematol. (1999a)
Haurie C., Person R., Dale D.C., Mackey M. (1999b). Haematopoietic dynamics in grey collies. Exper. Hematol. 27:1139–1148
Haurie C., Dale D.C., Rudnicki R., Mackey M.C. (2000). Modeling complex neutrophil dynamics in the grey collie. J. Theor. Biol. 204, 504–519
Iizuka Y., Horikoshi A., Sekiya S., Sawada U., Ohshima T., Amaki I. (1984). Periodic fluctuation of leukocytes, platelets and reticulocytes in a case of chronic myelocytic leukemia: The relation between leukocyte counts, cfu-c colony formation, csa and cia. Acta Haematol. Jpn. 47:71–79
Kennedy B.J. (1970). Cyclic leukocyte oscillations in chronic myelogenous leukemia during hydroxyurea therapy. Blood 35:751–760
Koury M. (1992). Programmed cell death (apoptosis) in hematopoiesis. Exp. Hematol. 20:391–394
Lomb N.R. (1976). Least-squares frequency analysis of unequally spaced data. Astrophys. Space Sci. 39:447–462
Morley, A. A., Baikie, A., Galton, D.: Cyclic leukocytosis as evidence for retention of normal homeostatic control in chronic granulocytic leukaemia. Lancet ?, 1320–1322 (1967)
Park J. (1996). Cytokine regulation of apoptosis in hematopoietic precursor cells. Curr. Opinion Hematol. 3:191–196
Rodriguez A.R., Lutcher C.L. (1976). Marked cyclic leukocytosis leukopenia in chronic myelogenous leukemia. Am. J. Med. 60:1041–1047
Umemura T., Hirata J., Kaneko S., Nishimura J., Motomura S., Kozuru M., Ibayashi H. (1986). Periodical appearance of erythropoietin-independent erythropoiesis in chronic myelogenous leukemia with cyclic oscillation. Acta Haematol. 76:230–234
Vodopick H., Rupp E.M., Edwards C.L., Goswitt G.A., Beauchamp J. (1972). Spontaneous cyclic leukocytosis and thrombocytosis in chronic granulocytic leukemia. New Eng. J. Med. 286:284–290
Williams G., Smith C. (1993). Molecular regulation of apoptosis: genetic controls on cell death. Cell 74:777–779
Williams G.T., Smith C.A., Spooncer E., Dexter T.M., Taylor D.R. (1990). Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis. Nature 353:76–78
Yamauchi K., Ide A. (1992). Spontaneous remission with cyclic leukocytosis in chronic myelogenous leukemia. Acta Haematol. 88:136–138
Author information
Authors and Affiliations
Corresponding author
Additional information
For Karl Hadeler, on his 70th birthday, leader, teacher, colleague and friend.
Rights and permissions
About this article
Cite this article
Colijn, C., Fowler, A.C. & Mackey, M.C. High frequency spikes in long period blood cell oscillations. J. Math. Biol. 53, 499–519 (2006). https://doi.org/10.1007/s00285-006-0027-9
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00285-006-0027-9