Document Detail

Chronic myeloid leukemia following therapy with imatinib mesylate (Gleevec). Bone marrow histopathology and correlation with genetic status.
MedLine Citation:
PMID:  12817431     Owner:  NLM     Status:  MEDLINE    
We evaluated bone marrow pathologic features and cytogenetic and molecular genetic status of 13 patients with interferon-resistant, chronic-phase chronic myeloid leukemia (CML), treated with imatinib mesylate (Gleevec). All had morphologic evidence of CML in the blood and bone marrow and were positive for bcr-abl by reverse transcriptase-polymerase chain reaction, fluorescence in situ hybridization (FISH), or both. Follow-up marrow biopsies, interphase FISH for bcr-abl, and conventional cytogenetics were performed at 3-month intervals (up to 24 months) after therapy initiation. All patients exhibited a reduction in bone marrow cellularity with decreases in myeloid/erythroid ratios at 3 to 6 months after therapy. The percentage of bcr-abl-positive cells by FISH decreased in all patients (pretherapy median, 73%; 3 months median, 47%). Cytogenetic and FISH data defined 2 groups after 6 months of follow-up: 5 patients became negative for bcr-abl by FISH; 8 remained positive, 4 of whom developed signs of clonal cytogenetic evolution. Patients who became negative for bcr-abl had no morphologic evidence of CML at 15 to 24 months of follow-up, whereas patients who remained positive redeveloped morphologic features of CML as cellularity increased. Some bcr-abl-positive patients showed signs of progression, including 2 patients who developed myeloid blast phase. Although all patients demonstrated an initial decrease in bone marrow cellularity after imatinib mesylate therapy, continued follow-up showed that histopathologic findings correlated with genetic response.
John L Frater; Martin S Tallman; Daina Variakojis; Brian J Druker; Debra Resta; Mary Beth Riley; Mary Ann Hrisinko; LoAnn C Peterson
Publication Detail:
Type:  Clinical Trial; Clinical Trial, Phase II; Journal Article; Multicenter Study    
Journal Detail:
Title:  American journal of clinical pathology     Volume:  119     ISSN:  0002-9173     ISO Abbreviation:  Am. J. Clin. Pathol.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-06-23     Completed Date:  2003-07-02     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0370470     Medline TA:  Am J Clin Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  833-41     Citation Subset:  AIM; IM    
Department of Pathology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
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MeSH Terms
Antineoplastic Agents / therapeutic use*
Bone Marrow / pathology*
Cytogenetic Analysis
Drug Resistance
Fusion Proteins, bcr-abl / genetics
Histiocytes / pathology
In Situ Hybridization, Fluorescence
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*,  genetics*,  pathology
Leukocyte Count
Megakaryocytes / pathology
Piperazines / therapeutic use*
Pyrimidines / therapeutic use*
Reticulin / analysis
Reverse Transcriptase Polymerase Chain Reaction
Reg. No./Substance:
0/Antineoplastic Agents; 0/Fusion Proteins, bcr-abl; 0/Piperazines; 0/Pyrimidines; 0/Reticulin; 152459-95-5/imatinib; 9008-11-1/Interferons

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