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Therapy-related changes of CD34+ progenitor cells in chronic myeloid leukemia: a morphometric study on sequential trephine biopsies.
- Source :
-
Journal of hematotherapy & stem cell research [J Hematother Stem Cell Res] 2001 Dec; Vol. 10 (6), pp. 827-36. - Publication Year :
- 2001
-
Abstract
- In chronic myeloid leukemia (CML), it has been assumed that the number of CD34(+) progenitor cells (PGCs) provides useful diagnostic and prognostic information regarding the evolution of accelerated phase and blastic crisis. However, until now no information is available about changes of this peculiar precursor cell population during therapy or possible associations with the other bone marrow constituents. For this reason, a retrospective clinicopathological study was performed on 83 patients with CML including 209 sequential bone marrow biopsies (intervals ranging between 6 and 143 months) and immunohistological staining of CD34(+) cells (QBEND10), megakaryocyte precursors (CD61), and erythropoiesis (Ret 40f). According to treatment modalities, three different groups of patients could be distinguished that received either monotherapy by interferon-alpha2b (IFN-alpha2b) or hydroxyurea (HU) and a combination of both. In comparison with a control group, morphometry revealed a significant increase in the quantity of CD34(+) PGCs per hematopoiesis (cellularity) in the CML bone marrow before treatment. Independently of treatment modalities and presentation of clinical findings nonresponding patients were generally characterized by a higher amount of progenitors in the initial biopsy specimens. Furthermore, calculation of the CD34(+) cell growth index showed a significant and rapid progression in nonresponding patients and in those developing an accelerated or blastic phase during therapy. This feature was prominently expressed following IFN treatment and related to a failing regeneration of nucleated erythroid precursors. In patients with a myelofibrotic bone marrow at onset no differences in the number of CD34(+) PGCs were recognizable in the pretreatment biopsies. This finding contrasted a significant and gradual change in progenitor cell frequency under treatment and evolving myelofibrosis. Opposed to HU therapy, the latter feature was explicitly detectable in the IFN group. In conclusion, the incidence of CD34(+) PGCs in the CML bone marrow reflects therapeutic efficacy. By demonstrating a significant relationship between fiber content and quantity of CD34(+) cells during treatment, experimental findings concerning the complex functional interactions between the fibrous stroma compartment and progenitor cell differentiation and proliferation are elucidated.
- Subjects :
- Antineoplastic Combined Chemotherapy Protocols administration & dosage
Biopsy
Bone Marrow Cells cytology
Case-Control Studies
Female
Hematopoiesis
Hematopoietic Stem Cells drug effects
Humans
Hydroxyurea administration & dosage
Hydroxyurea pharmacology
Interferon alpha-2
Interferon-alpha administration & dosage
Interferon-alpha pharmacology
Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
Male
Middle Aged
Primary Myelofibrosis pathology
Recombinant Proteins
Retrospective Studies
Therapeutic Equivalency
Time Factors
Antigens, CD34 analysis
Antineoplastic Combined Chemotherapy Protocols pharmacology
Hematopoietic Stem Cells cytology
Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1525-8165
- Volume :
- 10
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of hematotherapy & stem cell research
- Publication Type :
- Academic Journal
- Accession number :
- 11798509
- Full Text :
- https://doi.org/10.1089/152581601317210926