title: Chronic myeloid leukemia following therapy with imatinib mesylate (Gleevec). Bone marrow histopathology and correlation with genetic status.
abstract: 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.
authors.affiliation: Department of Pathology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Frater
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: Daina
authors.initials: D
authors.lastname: Variakojis
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Druker
authors.forename: Debra
authors.initials: D
authors.lastname: Resta
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Riley
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Hrisinko
authors.forename: LoAnn C
authors.initials: LC
authors.lastname: Peterson
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology*; D020732:Cytogenetic Analysis; D004351:Drug Resistance; D005355:Fibrosis; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006644:Histiocytes / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D007372:Interferons; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D007958:Leukocyte Count; D008533:Megakaryocytes / Q000473:pathology; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012155:Reticulin / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012155:Reticulin; D000068877:Imatinib Mesylate; D007372:Interferons; D016044:Fusion Proteins, bcr-abl