Document Detail


Bone marrow changes in chronic myelogenous leukaemia after long-term treatment with the tyrosine kinase inhibitor STI571: an immunohistochemical study on 75 patients.
MedLine Citation:
PMID:  15842636     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: To carry out an immunohistochemical study on bone marrow (BM) biopsy specimens in 75 patients with chronic myelogenous leukaemia (CML) on long-term STI571 therapy. METHODS AND RESULTS: Sequential BM specimens taken at intervals of 21 +/- 6 months were investigated by enzyme- and immunohistochemistry including proliferating cell nuclear antigen and apoptosis. Evaluation was performed either by semiquantitative scoring or by morphometry (CD61+ megakaryopoiesis). In 41 patients with chronic phase CML, treatment resulted in a significant decrease in cellularity and neutrophil granulopoiesis contrasting with an accumulation of erythroid precursor cells. Morphometry showed a reduction of abnormal micromegakaryocytes consistent with normalization. Regression of myelofibrosis was identified in eight of 15 patients, whereas progression occurred in 17 patients; mostly in those with acceleration and blastic crisis. The increased post-treatment incidence of reactive lymphoid nodules was remarkable. Myeloblasts, CD34+ progenitors and immature myelomonocytic cells initially decreased, but recurred in 14 patients who later developed a relapse. STI571 exerted an inhibitory effect on cell proliferation associated with enhanced apoptosis in responding patients. CONCLUSION: Long-term treatment with STI571 exerts pronounced changes on BM histopathology that not only involve haematopoiesis and stromal constituents, but also proliferation and apoptosis.
Authors:
J Thiele; H M Kvasnicka; A Schmitt-Graeff; S Kriener; K Engels; P Staib; E S Ollig; C Keller; S Fokkema; M Griesshammer; C F Waller; O G Ottmann; M L Hansmann
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Histopathology     Volume:  46     ISSN:  0309-0167     ISO Abbreviation:  Histopathology     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-21     Completed Date:  2005-05-31     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7704136     Medline TA:  Histopathology     Country:  England    
Other Details:
Languages:  eng     Pagination:  540-50     Citation Subset:  IM    
Affiliation:
Institutes of Pathology, University of Cologne, Germany. j.thiele@uni-koeln.de
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD34 / analysis
Antineoplastic Agents / therapeutic use
Biopsy
Bone Marrow Cells / chemistry,  drug effects,  pathology*
Female
Humans
Immunohistochemistry
Integrin beta3 / analysis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood*,  drug therapy,  pathology
Male
Middle Aged
Piperazines / therapeutic use*
Proliferating Cell Nuclear Antigen / analysis
Protein Kinase Inhibitors / therapeutic use
Protein-Tyrosine Kinases / antagonists & inhibitors*
Pyrimidines / therapeutic use*
Time Factors
Chemical
Reg. No./Substance:
0/Antigens, CD34; 0/Antineoplastic Agents; 0/Integrin beta3; 0/Piperazines; 0/Proliferating Cell Nuclear Antigen; 0/Protein Kinase Inhibitors; 0/Pyrimidines; 152459-95-5/imatinib; EC 2.7.10.1/Protein-Tyrosine Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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